Virus and Large Biological Complexes – Núria Verdaguer

Projects

• Structural and functional studies of viral RNA-dependent RNA polymerases and replication complexes

Most emerging and re-emerging human and animal viral diseases are associated with RNA viruses. One way to limit the impact of these pathogens is to prevent their replication and a thorough understanding of their replication and transcription machineries is therefore essential. Despite this group of viruses use different strategies for genome replication and transcription all RNA virus families depend on the activity of a virally encoded RNA-dependent RNA polymerase (RdRP). The structural information obtained for different RdRP and RdRP-RNA complexes contributed decisively to our knowledge about the functioning these enzymes. Despite the many clues provided by these structures there are still several gaps in our knowledge about the regulation of the RdRP activity and fidelity in different virus families.

We are combining structural data and functional studies to elucidate how RdRPs interact with RNA promotors, other viral proteins and cellular factors, to regulate replication and transcription activities in diferent viruses, including picornaviruses, flaviviruses, coronaviruses and filoviruses. This information will contribute decisively to our knowledge about the mechanisms of action of these enzymes, paving the way for the development of new therapeutic strategies against these pathogens.

• Protein-protein interactions in viral replication and pathogenesis

RNA viruses usually associate the RdRPs to other viral or host proteins as scaffold to form the replicative complexes in specific intracellular locations like the membranous compartments or inside capsids. The RdRP self-interactions to form dimers and higher order oligomers also play an important role in viral replication, contributing to the fine tuning of the polymerase activity, ensuring the proper levels of RNA production.

We have previous characterized the structure and quaternary arrangement of the  Methyltransferase-RdRP polypeptide NS5 from Zika virus (ZIKV), showing that this protein is able to form dimers and higher-order oligomers that regulate its enzymatic functions, as well as its association with other viral or host factors during infection. More recently we have shown that the multimeric arrangement of ZIKV-NS5 is required for nuclear exit, localization and interaction with primary cilium base proteins, and for promoting ciliopathy and premature neurogenesis. We have also showed that ZIKV-NS5 interacted with and depleted a number of cilia/the centrosome proteins (including, Rootletin, BART1, CEP164) and we aim to structurally and functionally characterize these interactions as new potential targets for therapeutic intervention.

• Structure and dynamics of viral capsids

We have previously characterized the early steps of human rhinovirus infection, including receptor binding by solving the first high resolution X-ray structures of a human minor group rhinovirus (RV1A) bound to its cellular receptor protein. We have also determined the structural rearrangements occurring in the RV1A capsid trapped in the process of RNA uncoating. We are currently studying the structural dynamics of other RV capsids,  including the effect of a number of capsid binders as antiviral candidates, preventing RNA uncoating.

• Structural dynamics of the vault shell

Vaults are ubiquitous ribonucleoprotein particles involved in a diversity of cellular processes, with promising applications as nanodevices for delivery of multiple cargos. The vault shell is assembled by the symmetrical association of multiple copies of the major vault protein that, initially, generates half vaults. The pairwise, anti-parallel association of two half vaults produces the whole particle. Using a combination of biophysical and  structural techniques with the production of recombinant mutant vaults, we aim to decipher the principles of vault dynamics and opening.

Lab people

Selected publications

Structural insights on the nucleoprotein C-terminal domain of Měnglà virus

Ferrero DS, Tomás Gilabert O, Verdaguer N.

Microbiol Spectr 2023 11:e02373-23. doi: 10.1128/spectrum.02373-23.

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Symmetry disruption commits vault particles to disassembly.

Guerra P, González-Alamos M, Llauró A, Casañas A, Querol-Audí J, de Pablo PJ, Verdaguer N.

Sci Adv. 2022 Feb 11;8(6):eabj7795. doi: 10.1126/sciadv.abj7795.

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Multimerization of Zika Virus-NS5 Causes Ciliopathy and Forces Premature Neurogenesis.

Saade M, Ferrero DS, Blanco-Ameijeiras J, Gonzalez-Gobartt E, Flores-Mendez M, Ruiz-Arroyo VM, Martínez-Sáez E, Ramón Y Cajal S, Akizu N, Verdaguer N, Martí E. Cell Stem Cell. 2020 Dec 3;27(6):920-936.e8. doi: 10.1016/j.stem.2020.10.002.

Highlighted in Nature Rev Microbiol https://www.nature.com/articles/s41579-020-00481-9

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Supramolecular arrangement of the full-length Zika virus NS5.

Ferrero DS, Ruiz-Arroyo VM, Soler N, Usón I, Guarné A, Verdaguer N.

PLoS Pathog. 2019 Apr 5;15(4):e1007656.

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Structural characterization of the Rabphilin-3A-SNAP25 interaction.

Ferrer-Orta C, Pérez-Sánchez MD, Coronado-Parra T, Silva C, López-Martínez D, Baltanás-Copado J, Gómez-Fernández JC, Corbalán-García S, Verdaguer N.

Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):E5343-E5351.

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The Structure of the RNA-Dependent RNA Polymerase of a Permutotetravirus Suggests a Link between Primer-Dependent and Primer Independent Polymerases

Ferrero DS, Buxaderas M, Rodríguez JF, Verdaguer N.

PLoS Pathog. 2015 Dec 1;11(12):e1005265.

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Structural insights into the Ca2+ and PI(4,5)P2 binding modes of the C2 domains of rabphilin 3A and synaptotagmin 1

Guillén J, Ferrer-Orta C, Buxaderas M, Pérez-Sánchez D, Guerrero-Valero M, Luengo-Gil G, Pous J, Guerra P, Gómez-Fernández JC, Verdaguer N*, Corbalán-García S* (*corresponding Authors).

Proc Natl Acad Sci USA. 2013 Dec 17;110(51):20503-8.

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Uncoating of common cold virus is preceded by RNA switching as determined by X-ray and cryo-EM analyses of the subviral A-particle

Pickl-Herk A, Luque D, Vives-Adrián L, Querol-Audí J, Garriga D, Trus BL, Verdaguer N*, Blaas D*, Castón JR* (*corresponding Authors).

Proc Natl Acad Sci USA.2013 Dec 10;110(50):20063-8.

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Insights into minor group rhinovirus uncoating: the X-ray structure of the HRV2 empty capsid

Garriga D, Pickl-Herk A, Luque D, Wruss J, Castón JR, Blaas D, Verdaguer N.

PLoS Pathog. 2012 Jan;8(1):e1002473.

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The mechanism of vault opening from the high resolution structure of the N-terminal repeats of MVP

Querol-Audí J, Casañas A, Usón I, Luque D, Castón JR, Fita I, Verdaguer N.

EMBO J. 2009 Nov 4;28(21):3450-7.

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Structural and mechanistic insights into the association of PKCalpha-C2 domain to PtdIns(4,5)P2

Guerrero-Valero M, Ferrer-Orta C, Querol-Audí J, Marin-Vicente C, Fita I, Gómez-Fernández JC, Verdaguer N*, Corbalán-García S*(*corresponding authors).

Proc Natl Acad Sci USA. 2009 Apr 21;106(16):6603-7.

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Activation mechanism of a noncanonical RNA-dependent RNA polymerase

Garriga D, Navarro A, Querol-Audí J, Abaitua F, Rodríguez JF, Verdaguer N.

Proc Natl Acad Sci. USA. 2007;104:20540-5.

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Sequential structures provide insights into the fidelity of RNA replication

Ferrer-Orta C, Arias A, Perez-Luque R, Escarmis C, Domingo E, Verdaguer N.

Proc Natl Acad Sci. USA. 2007;104:9463-8

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The structure of a protein primer-polymerase complex in the initiation of genome replication

Ferrer-Orta C, Arias A, Agudo R, Perez-Luque R, Escarmis C, Domingo E, Verdaguer N.

EMBO J. 2006 Feb 22;25(4):880-8.

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X-ray structure of a minor group human rhinovirus bound to a fragment of its cellular receptor protein

Verdaguer N, Fita I, Reithmayer M, Moser R, Blaas D.

Nat Struct Mol Biol. 2004; 11:429-34.

All publications

Ferrero DS, Ruiz-Arroyo VM, Soler N, Usón I, Guarné A, Verdaguer N.

PLoS Pathog. 2019 Apr 5;15(4):e1007656.

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Contribution of a Multifunctional Polymerase Region of Foot-and-Mouth Disease Virus to Lethal Mutagenesis.

de la Higuera I, Ferrer-Orta C, Moreno E, de Ávila AI, Soria ME, Singh K, Caridi F, Sobrino F, Sarafianos SG, Perales C, Verdaguer N, Domingo E.

J Virol. 2018 Sep 26;92(20). pii: e01119-18. doi: 10.1128/JVI.01119-18.

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Viral RNA-Dependent RNA Polymerases: A Structural Overview

Ferrero D, Ferrer-Orta C, Verdaguer N.

Subcell Biochem. 2018;88:39-71.

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Structural characterization of the Rabphilin-3A-SNAP25 interaction.

Ferrer-Orta C, Pérez-Sánchez MD, Coronado-Parra T, Silva C, López-Martínez D, Baltanás-Copado J, Gómez-Fernández JC, Corbalán-García S, Verdaguer N.

Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):E5343-E5351.

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Structure of eIF4E in Complex with an eIF4G Peptide Supports a Universal Bipartite Binding Mode for Protein Translation.

Miras M, Truniger V, Silva C, Verdaguer N, Aranda MA, Querol-Audí J.

Plant Physiol. 2017 Jul;174(3):1476-1491

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Structural basis for biologically relevant mechanical stiffening of a virus capsid by cavity-creating or spacefilling mutations.

Guerra P, Valbuena A, Querol-Audí J, Silva C, Castellanos M, Rodríguez-Huete A, Garriga D, Mateu MG, Verdaguer N.

Sci Rep. 2017 Jun 22;7(1):4101.

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Molecular and Functional Bases of Selection against a Mutation Bias in an RNA Virus.

de la Higuera I, Ferrer-Orta C, de Ávila AI, Perales C, Sierra M, Singh K, Sarafianos SG, Dehouck Y, Bastolla U, Verdaguer N, Domingo E.

Genome Biol Evol. 2017 May 1;9(5):1212-1228.

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The Decrease in pH destabilizes individual vault nanocages by weakening the inter-protein lateral interaction

Llauró A, Guerra P, Kant R, Bothner B, Verdaguer N.

Sci Rep. 2016 Oct 14:6:34143.

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Both cis and trans Activities of Foot-and-Mouth Disease Virus 3D Polymerase Are Essential for Viral RNA Replication.

Herod MR, Ferrer-Orta C, Loundras EA, Ward JC, Verdaguer N, Rowlands DJ, Stonehouse NJ.

J Virol. Jul 11;90(15):6864-83. (2016)

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The Structure of the RNA-Dependent RNA Polymerase of a Permutotetravirus Suggests a Link between Primer-Dependent and Primer-Independent Polymerases.

Ferrero DS, Buxaderas M, Rodríguez JF, Verdaguer N.

PLoS Pathog. Dec 1;11(12):e1005265. (2015)

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Infectious Bursal Disease Virus VP3 Upregulates VP1-Mediated RNA-Dependent RNA Replication.

Ferrero D, Garriga D, Navarro A, Rodríguez JF, Verdaguer N.

J Virol. Nov;89(21):11165-8. (2015)

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RNA-Dependent RNA Polymerases of Picornaviruses: From the Structure to Regulatory Mechanisms.

Ferrer-Orta C, Ferrero D, Verdaguer N.

Viruses. Aug 6;7(8):4438-60. (2015)

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Multifunctionality of a picornavirus polymerase domain: nuclear localization signal and nucleotide recognition

Ferrer-Orta C, de la Higuera I, Caridi F, Sánchez-Aparicio MT, Moreno E, Perales C, Singh K, Sarafianos SG, Sobrino F, Domingo E, Verdaguer N.

J Virol. Apr 22. pii: JVI.03283-14. (2015)

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The RNA template channel of the RNA-dependent RNA polymerase as a target for development of antiviral therapy of multiple genera within a virus family.

Van der Linden L, Vives-Adrián L, Selisko B, Ferrer-Orta C, Liu X, Lanke K, Ulferts R, De Palma AM, Tanchis F, Goris N, Lefebvre D, De Clercq K, Leyssen P, Lacroix C, Pürstinger G, Coutard B, Canard B, Boehr DD, Arnold JJ, Cameron CE, Verdaguer N, Neyts J, van Kuppeveld FJ.

PLoS Pathog. Mar 23;11(3):e1004733. (2015)

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Structural basis for host membrane remodeling induced by protein 2B  of hepatitis A virus.

Vives-Adrián L, Garriga D, Buxaderas M, Fraga J, Pereira PJ, Macedo-Ribeiro S, Verdaguer N.

J Virol. Apr;89(7):3648-58. (2015)

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A novel benzonitrile analogue inhibits rhinovirus replication.

Verdaguer N, Ferrero D, Murthy MR. Viruses and viral proteins.

IUCrJ. Oct 14;1(Pt 6):492-504. (2014)

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A novel benzonitrile analogue inhibits rhinovirus replication

Lacroix C, Querol-Audí J, Roche M, Franco D, Froeyen M, Guerra P, Terme T,Vanelle P, Verdaguer N, Neyts J, Leyssen P.

J Antimicrob Chemother. Oct;69(10):2723-32. (2014)

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Cryo-EM near-atomic structure of a dsRNA fungal virus shows ancient structural motifs preserved in the dsRNA viral lineage.

Luque D, Gómez-Blanco J, Garriga D, Brilot AF, González JM, Havens WM, Carrascosa JL, Trus BL, Verdaguer N, Ghabrial SA, Castón JR.

Proc Natl Acad Sci USA. May 27;111(21):7641-6. (2014)

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The crystal structure of a cardiovirus RNA-dependent RNA polymerase reveals an unusual conformation of the polymerase active site.

Vives-Adrian L, Lujan C, Oliva B, van der Linden L, Selisko B, Coutard B, Canard B, van Kuppeveld FJ, Ferrer-Orta C, Verdaguer N.

J Virol. May;88(10):5595-607. (2014)

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Mechanical stability and reversible fracture of vault particles.

Llauró A, Guerra P, Irigoyen N, Rodríguez JF, Verdaguer N, de Pablo PJ.

Biophys J. Feb 4;106(3):687-95. (2014)

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Structural insights into the Ca2+ and PI(4,5)P2 binding modes of the C2 domains of rabphilin 3A and synaptotagmin 1.

Guillén J, Ferrer-Orta C, Buxaderas M, Pérez-Sánchez D, Guerrero-Valero M, Luengo-Gil G, Pous J, Guerra P, Gómez-Fernández JC, Verdaguer N*, Corbalán-García S* (*corresponding Authors).

Proc Natl Acad Sci USA. Dec17;110(51):20503-8. (2013)

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Uncoating of common cold virus is preceded by RNA switching as determined by X-ray and cryo-EM analyses of the subviral A-particle.

Pickl-Herk A, Luque D, Vives-Adrián L, Querol-Audí J, Garriga D, Trus BL, Verdaguer N*, Blaas D*, Castón JR* (*corresponding Authors).

Proc Natl Acad Sci USA. Dec 10;110(50):20063-8. (2013)

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X-ray crystallography of viruses.

Verdaguer N, Garriga D, Fita I.

Subcell Biochem. 68:117-44. (2013)

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New features of vault architecture and dynamics revealed by novel refinement using the deformable elastic network approach.

Casañas A, Querol-Audí J, Guerra P, Pous J, Tanaka H, Tsukihara T, Verdaguer N*, Fita I* (*corresponding authors).

Acta Crystallogr D BiolCrystallogr. Jun;69(Pt6):1054-61. (2013)

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Role of motif B loop in allosteric regulation of RNA-dependent RNA polymerization activity.

Garriga D, Ferrer-Orta C, Querol-Audí J, Oliva B, Verdaguer N.

J Mol Biol. Jul 10;425(13):2279-87. (2013)

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Purification, crystallization and preliminary X-ray diffraction analysis of the RNA-dependent RNA polymerase from Thosea asigna virus.

Ferrero D, Buxaderas M, Rodriguez JF, Verdaguer N.

Acta Crystallogr Sect F Struct Biol Cryst Commun. Oct 1;68(Pt 10):1263-6. (2012)

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Conformational changes in motif D of RdRPs as fidelity determinant.

Verdaguer N, Ferrer-Orta C.

Structure. Sep 5;20(9):1448-50. (2012)

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Vault particles: a new generation of delivery nanodevices.

Casañas A, Guerra P, Fita I, Verdaguer N.

Curr Opin Biotechnol. Dec;23(6):972-7 (2012)

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Epitope insertion at the N-terminal molecular switch of the rabbit hemorrhagic disease virus T = 3 capsid protein leads to larger T = 4 capsids.

Luque D, González JM, Gómez-Blanco J, Marabini R, Chichón J, Mena I, Angulo I, Carrascosa JL, Verdaguer N, Trus BL, Bárcena J, Castón JR.

J Virol. Jun;86(12):6470-80. (2012)

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Insights into minor group rhinovirus uncoating: the X-ray structure of the HRV2 empty capsid.

Garriga D, Pickl-Herk A, Luque D, Wruss J, Castón JR, Blaas D, Verdaguer N.

PLoS Pathog. Jan;8(1):e1002473. (2012)

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Cloning, purification and preliminary crystallographic studies of the 2AB protein from hepatitis A virus.

Garriga D, Vives-Adrián L, Buxaderas M, Ferreira-da-Silva F, Almeida B, Macedo-Ribeiro S, Pereira PJ, Verdaguer N.

Acta Crystallogr Sect F Struct Biol Cryst Commun. Oct 1;67(Pt 10):1224-7. (2011)

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A multi-step process of viral adaptation to a mutagenic nucleoside analogue by modulation of transition types leads to extinction-escape.

Agudo R, Ferrer-Orta C, Arias A, de la Higuera I, Perales C, Pérez-Luque R, Verdaguer N, Domingo E.

PLoS Pathog. Aug 26;6(8):e1001072. (2010)

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The T=1 capsid protein of Penicillium chrysogenum virus is formed by a repeated helix-rich core indicative of gene duplication.

Luque D, González JM, Garriga D, Ghabrial SA, Havens WM, Trus B, Verdaguer N, Carrascosa JL, Castón JR.

J Virol. Jul;84(14):7256-66. (2010)

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Structure of foot-and-mouth disease virus mutant polymerases with reduced sensitivity to ribavirin.

Ferrer-Orta C, Sierra M, Agudo R, de la Higuera I, Arias A, Pérez-Luque R, Escarmís C, Domingo E, Verdaguer N.

J Virol. Jun;84(12):6188-99. (2010)

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Structural insights into replication initiation and elongation processes by the FMDV RNA-dependent RNA polymerase.

Ferrer-Orta C, Agudo R, Domingo E, Verdaguer N.

Curr Opin Struct Biol. Dec;19(6):752-8. (2009)

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The mechanism of vault opening from the high resolution structure of the N-terminal repeats of MVP.

Querol-Audí J, Casañas A, Usón I, Luque D, Castón JR, Fita I, Verdaguer N.

EMBO J. Nov 4;28(21):3450-7. (2009)

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Structural and mechanistic insights into the association of PKCalpha-C2 domain to PtdIns(4,5)P2.

Guerrero-Valero M, Ferrer-Orta C, Querol-Audí J, Marin-Vicente C, Fita I, Gómez-Fernández JC, Verdaguer N*, Corbalán-García S*(*corresponding authors).

Proc Natl Acad Sci USA. Apr 21;106(16):6603-7. (2009)

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Autoproteolytic activity derived from the infectious bursal disease virus capsid protein.

Irigoyen N, Garriga D, Navarro A, Verdaguer N, Rodríguez JF, Castón JR.

J Biol Chem. Mar 20;284(12):8064-72. (2009)

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Minor group human rhinovirus-receptor interactions: geometry of multimodular attachment and basis of recognition

Querol-Audí J, Konecsni T, Pous J, Carugo O, Fita I, Verdaguer N, Blaas D.

FEBS Lett. Jan 5;583(1):235-40. (2009)

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Structural insights into the multifunctional protein VP3 of birnaviruses.

Casañas A, Navarro A, Ferrer-Orta C, González D, Rodríguez JF, Verdaguer N.

Structure. 16:29-37. (2008)

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Activation mechanism of a noncanonical RNA-dependent RNA polymerase.

Garriga D, Navarro A, Querol-Audí J, Abaitua F, Rodríguez JF, Verdaguer N.

Proc Natl Acad Sci. USA. 104:20540-5. (2007)

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Sequential structures provide insights into the fidelity of RNA replication.

Ferrer-Orta C, Arias A, Perez-Luque R, Escarmis C, Domingo E, Verdaguer N.

Proc Natl Acad Sci. USA. 104:9463-8 (2007)

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Infectious bursal disease virus capsid assembly and maturation by structural rearrangements of a transient molecular switch.

Luque D, Saugar I, Rodriguez JF, Verdaguer N, Garriga D, Martin CS, Velazquez-Muriel JA, Trus BL, Carrascosa JL, Caston JR.

J Virol. 81:6869-78. (2007)

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The 2.6-Angstrom structure of infectious bursal disease virus-derived T=1 particles reveals new stabilizing elements of the virus capsid.

Garriga D, Querol-Audi J, Abaitua F, Saugar I, Pous J, Verdaguer N, Caston JR, Rodriguez JF.

J Virol. 80:6895-905. (2006)

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The structure of a protein primer-polymerase complex in the initiation of genome replication.

Ferrer-Orta C, Arias A, Agudo R, Perez-Luque R, Escarmis C, Domingo E, Verdaguer N.

EMBO J. Feb 22;25(4):880-8. (2006)

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A comparison of viral RNA-dependent RNA polymerases.

Ferrer-Orta C, Arias A, Escarmis C, Verdaguer N.

Curr Opin Struct Biol. 16:27-34. (2006)

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Mutant viral polymerase in the transition of virus to error catastrophe identifies a critical site for RNA binding

Arias A, Agudo R, Ferrer-Orta C, Perez-Luque R, Airaksinen A, Brocchi E, Domingo E, Verdaguer N, Escarmis C.

J Mol Biol. 353:1021-32. (2005)

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Preliminary analysis of two and three dimensional crystals of vault ribonucleoprotein particles.

Querol-Audi J, Perez-Luque R, Fita I, Lopez-Iglesias C, Caston JR, Carrascosa JL, Verdaguer N.

J Struct Biol. 151:111-5. (2005)

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Structure of foot-and-mouth disease virus RNA-dependent RNA polymerase and its complex with a template-primer RNA.

Ferrer-Orta C, Arias A, Perez-Luque R, Escarmis C, Domingo E, Verdaguer N.

J Biol Chem. 279:47212-21. (2004)

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X-ray structure of a minor group human rhinovirus bound to a fragment of its cellular receptor protein

Verdaguer N, Fita I, Reithmayer M, Moser R, Blaas D.

Nat Struct Mol Biol. 11:429-34. (2004)

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The coat protein of Rabbit hemorrhagic disease virus contains a molecular switch at the N-terminal region facing the inner surface of the capsid.

Barcena J, Verdaguer N, Roca R, Morales M, Angulo I, Risco C, Carrascosa JL, Torres JM, Caston JR.

Virology. 322:118-34. (2004)

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Crystallization and preliminary X-ray analysis of the glycogen synthase from Pyrococcus abyssi.

Horcajada C, Cid E, Guinovart JJ, Verdaguer N, Ferrer JC.

Acta Crystallogr D Biol Crystallogr. 59:2322-4. (2003)

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Evolution of cell recognition by viruses: a source of biological novelty with medical implications.

Baranowski E, Ruiz-Jarabo CM, Pariente N, Verdaguer N, Domingo E.

Adv Virus Res. 62:19-111. (2003)

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Structure of swine vesicular disease virus: mapping of changes occurring during adaptation of human coxsackie B5 virus to infect swine.

Verdaguer N, Jimenez-Clavero MA, Fita I, Ley V.

J Virol 77:9780-9. (2003)

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Retinoic acid binds to the C2-domain of protein kinase C(alpha).

Ochoa WF, Torrecillas A, Fita I, Verdaguer N, Corbalan-Garcia S, Gomez-Fernandez JC.

Biochemistry. 42:8774-9. (2003)

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Crystallization and preliminary X-ray analysis of swine vesicular disease virus (SVDV).

Jimenez-Clavero MA, Ley V, Fita I, Verdaguer N.

Acta Crystallogr D Biol Crystallogr. 59:541-3. (2003)

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Additional binding sites for anionic phospholipids in the crystal structures of complexes of the C2 domain of Protein Kinase Ca.

W.F.Ochoa, S. Corbalan-Garcia, R. Eritja, J.C. Gomez-Fernandez, I. Fita & N.Verdaguer

J. Mol. Biol. 320:277-291. (2002)

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Probing degeneracy in antigen-antibody recognition at the immunodominant site of foot-and-mouth disease virus.

P.Gomes, W. F., Ochoa, N.Verdaguer, E. Giralt and D. Andreu.

J. Pep. Res. 59: 221-231. (2003)

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Structure of the C2 domain from novel Protein Kinase Cε: a membrane binding model for Ca2+ -independent PKCs.

W.F.Ochoa, J. Garcia-Garcia, I. Fita, S. Corbalan-Garcia, N. Verdaguer, J.C. Gomez-Fernandez.

J. Mol. Biol. 311:837-849 (2001)

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Crystallization and preliminary X-ray analysis of Clade I catalases from Pseudomonas syringae and  Listeria seeligeri

R. Perez-Luque, X.Carpena., W.F. Ochoa., N. Verdaguer., W. Melik-Adamyan, M. Klotz, J. Switala, I. Fita. & P.Loewen.

Acta Cryst. 2001; D57: 1184-1186. (2001)

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The need for a shared database infrastructure: combining X-ray crystallography and electron microscopy

S.G. Kalko, M. Chagoyen, N. Jimenez-Lozano, N. Verdaguer, I. Fita., J.M. Carazo.

Eur. Biophys J. 29: 457-462 (2000)

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A multiply substituted G-H loop from foot-and-mouth disease virus in complex with a neutralising antibody: a role for water molecules

W.F.Ochoa, S. Kalko, M.G.Mateu, P.Gomes, D.Andreu, E.Domingo, I.Fita and N.Verdaguer.

J.Gen.Virol. 81: 1495-1505. (2000)

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Structure of human rhinovirus serotype 2 (HRV2)

N.Verdaguer, D.Blaas, I.Fita.

J. Mol. Biol. 300:1179-1194. (2000)

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Flexibility of the major antigenic loop of foot-and-mouth disease virus bound to an Fab fragment of a neutralizing antibody: Structure and Neutralisation.

N.Verdaguer, G.Schoehn, W.F.Ochoa, I.Fita, S.Brooks, A.King, E.Domingo, M.G.Mateu, D.Stuart, E.Hewat.

Virology 255:260-268. (1999)

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Crystallization and preliminar x-ray analysis of human rhinovirus serotype 2 (HRV2).

N.Verdaguer, T. Marlovits, J.Bravo, D.Stuart, D.Blaas and I.Fita.

Acta Cryst D54:1459-1461. (1999)

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Ca2+ bridges the membrane-binding domain C2 od Protein Kinase Ca directly tom phosphatidylserine

N.Verdaguer, S. Corbalan-Garcia, W.F. Ochoa, I. Fita, J.C. Gomez-Fernandez.

EMBO J. 18: 6329-6338. (1999)

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Biochemical and structural studies with neutralizing antibodies raised against foot-and-mouth disease virus

E.Domingo, N. Verdaguer, W.F.Ochoa, C.M. Ruiz-Jarabo,N. Sevilla, E.Baranowski, D.Andreu, M.G.Mateu, I.Fita.

Virus Research 62: 169-175. (1999)

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A Similar Pattern of Interaction for Different Antibodies with a Major Antigenic Site of Foot-and-Mouth Disease Virus: Implications for Intratypic Antigenic Variation

N. Verdaguer, N. Sevilla, M.L. Valero, D. Stuart, E. Brocchi, D. Andreu, E. Giralt, E. Domingo, M. Mateu and I.Fita.

J Virol 72:739-748. (1998)

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Multiple Virulence Determinants of Foot-and-Mouth Disease Virus in Cell Culture

E.Baranowski, N. Sevilla, N.Verdaguer, C.M. Ruiz-Jarabo, E.Beck, E.Domingo

JVirol 72:6362-6372. (1998)

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Rapid selection in modified BHK-21 cells of Foot-and-Mouth  Disease Virus variant showing alterations in cell tropism.

C.Escarmís, E.C. Carrillo, M.Ferrer, J.F.Garcia Arriaza, N. López, Cecilia Tami, N. Verdaguer, E.Domingo and  M.T.Fanze-Fernandez.

J Virol 72:10171-10179. (1998)

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Structure of the complex of an Fab fragment of a neutralising  antibody with foot-and-mouth disease virus: Positioning of a highly mobile antigenic loop

E.A. Hewat, N. Verdaguer, I.Fita, W. Blakemore, S. Brookers, A. King, J. Newman, E. Domingo, M.G. Mateu, D. Stuart.

EMBO Journal 16:1492-1500. (1997)

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Evolution subverting essential: Dispensability of the cell attachament Arg-Gly-Asp motif in multiply passaged foot-and-mouth disease virus.

M.A.Martinez, N.Verdaguer, M.G.Mateu, E.Domingo

Proc Natl Acad Sci USA. 94:6798-6802. (1997)

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Efficient Neutralization of Foot-and-Mouth Disease Virus by Monovalent Antibody Binding.

N.Verdaguer, I.Fita, E.Domingo, M.G.Mateu.

J Virol 71: 9813-9816. (1997)

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Structural variability of A-DNA in crystals of the octamer d(pCpCpCpGpCpGpGpG).

L.M.Gonzaga, J.A. Subirana, N.Verdaguer, D. Pyshnyi, L.Campos, L. Malinina.

Journal of Biomolecular Structure and dynamics 15:151-163. (1997)

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Structure and supramolecualr Packing features of the dipeptide Arg-Val acetate.

R.Recacha, N. Verdaguer and J.A. Subirana.

Int. J. pept. Prot. Res. 50:388-392. (1997)

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Induced Pocket to Accomodate the Cell Attachment Arg-Gly-Asp Motif in a Neutralizing Antibody Against Foot-and-Mouth-Disease Virus.

N.Verdaguer, M.G.Mateu, J.Bravo, E.Domingo, I.Fita.

J Mol Biol, 256:364-376. (1996)

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Molecular Evolution of Aphthoviruses.

1. Domingo, M.G.Mateu, C. Escarmis, E.Martínez-Salas, D.Andreu, E. Giralt, N. Verdaguer, I.Fita.

Virus Genes 11:197-207. (1996)

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Crystallization and preliminary X-ray diffraction studies of the Lb proteinase from foot-and-mouth disease virus.

A.Guarné, R.Kirchweger, N.Verdaguer, H-D.Liebig, D.Blaas, T.Skern, I.Fita.

Protein Science 5:1931-1933. (1996)

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Antigenically Profound Amino Acid Substitutions Occur During Large Population Passages of Foot-and-Mouth Disease Virus.

N.Sevilla, N.Verdaguer, E.Domingo.

Virology 225:400-405. (1996)

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Structure of the major antigenic loop of foot-and-mouth disease virus complexed with a neutralizing antibody:  direct involvement of the Arg-Gly-Asp motif in the interaction

N. Verdaguer, M.G. Mateu, D. Andreu, E. Giralt, E. Domingo, I.Fita.

EMBO Journal 14: 1690-1696. (1995)

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Crystal structure of catalase HPII from Escherichia coli.

J. Bravo, N. Verdaguer, J. Tormo, C. Betzel, J. Switala, P.C. Loewen, I.Fita.

Structure 3:491-502. (1995)

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Cyclic peptides as conformationally restricted models of viral antigens: application to foot-and-mouth disease virus.

M.L. Valero, J.A. Camarero, A. Adeva, N. Verdaguer, I.Fita, M.G. Mateu, E. Domingo, E. Giralt, D. Andreu.

Biomedical Peptides, Proteins & Nucleic Acids 1:133-140. (1995)

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Crystallization and Preliminary X-Ray Diffraction Studies of a Monoclonal Antibody Fab Fragment Against Foot-and-Mouth Disease Virus and of Its Complex With the Main Antigenic Site Peptide.

N. Verdaguer, M.G. Mateu, J. Bravo, J. Tormo, E. Giralt, D. Andreu, E. Domingo, I.Fita.

Proteins: Structure, Function and Genetics 18:201-203. (1994)

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Structure of the dipeptide L-lysine-L-leucine. Acetate, 0.5 acetic acid hemihydrate.

M. Perelló, N. Verdaguer, J. Aymami, I.Fita.

Journal of Chemical Crystallography 24:597-602. (1994)

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Molecular structure of the A-tract DNA dodecamer d(CGCAAATTTGCG) complexed with the minor groove binding drug netropsin.

L.Tabernero, N.Verdaguer, M.Coll,,G.A. van der Marel, J.H.van Boom, A.Rich and J.Aymamí.

Biochemistry  32:8403-8410. (1993)

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Helical structure of basic proteins from spermatozoa. Comparison with model peptides.

N. Verdaguer, M. Perelló, J. Palau and J. A. Subirana.

Eur. J. Biochemistry 214:879-887. (1993)

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A and Z canonical conformations in d(CnGCGn) crystals characterized by microraman spectroscopies.

H.Sfihi, J. Liquier, L. Urpí, N. Verdaguer, J.A. Subirana, J. Igolen and E. Taillandier

Biopolymers 33:1715-1723. (1993)

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Structure of trans-diaquabis[(2-oxopyrrolidin-1-yl)acetamide]copper(II) perchlorate.

X. de la Cruz, A. Martinez-Balbás, J. Tormo and N. Verdaguer.

Acta cryst. C48:167-169. (1992)

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Synthesis of bis(pentachlorophenyl) silanediol and related compounds. Crystal structure of diethoxybis(pentachlorophenyl) silane.

Ll.Fajarí, J.Riera, Ll.Juliá ,J.Lloveras, N.Verdaguer and I.Fita.

J.Organometalics Chemistry 423:163-171. (1992)

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Molecular structure of a complete turn of A-DNA.

N.Verdaguer, D.Fernández, J.Aymamí, I.Fita, M. Coll T.Huynh-Dinh, J.Igolen and J.A.Subirana

J.Mol. Biol. 221:623-625. (1991)

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Molecular Structure of L-Lysyl-L-Tyrosyl-L-Serine Acetate.

N.Verdaguer, I.Fita and J.A.Subira.

Int J Biol Macromol. 12:315-320. (1990)

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Crystal and Molecular Structure of L-Lysyl-L-Valine Hydrochloride a new Lysine Conformation.

Ll.Boqué, N.Verdaguer, L.Urpí, I.Fita and J.A.Subirana.

Int.J.Peptide and Protein Res. 33:157-161. (1989)

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Conformations in crystals and solutions of d(CACGTG), d(CCGCGG) and d(GGCGCC) studied by vibrational spectroscopy.

L.Urpí, J.P.Ridoux, J.Liquier, N.Verdaguer, I.Fita, J.A.Subirana, F.Iglesias, T.Huynh-Dinh, J.Igolen and E.Taillandier.

Nucleic Acids Res. 17:6669-6680. (1989)

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Molecular Structure of L-Lysyl-L-Alanyl-L-Alanine. A tripeptide found  in Histone H1

N.Verdaguer, L.Urpí, I.Fita, and J.A.Subirana.

Biopolymers. 27:1887-1896. (1988)

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Book Chapters

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Modificación de la Densidad Electrónica en el Afinamiento y Extensión de las Fases en Macromoléculas.

J. Bravo, N. Verdaguer, I.Fita.

Nuevas Tendencias en Cristalografía. Consejo Superior de Investigaciones Científicas, Madrid, 1995.

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Aportaciones de la cristalografía al estudio del ADN.

J.A. Subirana, X. Salas, L.Urpí E. Font, N. Verdaguer.

Nuevas Tendencias en Cristalografía. Consejo Superior de Investigaciones Científicas, Madrid, 1995.

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Cristalografía de Macromoléculas

I.Fita, J. Bravo, N. Verdaguer

Simulación Molecular y Ciencias de Materiales. Ed. Bernardo Celda. Universidad Menéndez y Pelayo, Valencia. (1995)

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Cristal.lografia de Proteïnes

A. Guasch, N.Verdaguer, X.Gomis-Rüth, I.Fita and M.Coll

Dinàmica estructural de Macromolècules. Trb. Soc. Cat. Biol. 48,. Ll.Cornudella Ed. (1999)

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Estructura de grandes agregados moleculares: estudios combinados de cristalografia de rayos-X y microscopia electrónica

N. Verdaguer, W.F.Ochoa, D. Blaas, E. Hewat and I. Fita.

Trb. Soc. Cat. Biol. 53 115-124. (2002)

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Handbook of Metalloproteins C2 domains

N.Verdaguer, I.Fita, M.Senena-Corbalan, J.C.Gomez-Fernandez

John Wiley & Sons, Ltd. Eds. A. Messerschmidt, R. Huber, T. Poulos and K. Wieghardt. (2003)

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Functional and Structural Aspects of the Interaction of Foot-and-Mouth Disease Virus with Antibodies

M.G.Mateu & N. Verdaguer.

In Foot-and-mouth disease current perspectives. Horizon Bioscience. Eds. F. Sobrino and E. Domingo. (2004)

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RNA Virus Polymerases. In Viral Genome Replication. II. Elements, factors and enzymes: Structure-function and mechanism.

C. Ferrer-Orta, N. Verdaguer Cameron, Götte and Raney eds.

Springer, New York, (2009)

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Mutation, Quasispecies and Lethal Mutagenesis in Picornaviruses.

Domingo E, Perales C, Agudo R, Arias A, Escarmís C, Ferrer-Orta C, Verdaguer N. Ehrenfeld, Domingo and Roos eds.

ASM Press, Washington DC. (2010)

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Structural Dynamics of Picornaviral RdRP Complexes. Implications for the Design of Antivirals

Verdaguer N. Ferrer-Orta C, Domingo, E, M.A. Carrondo and P. Spadon (eds)

Springer Science+Business Media B.V. (2012)

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Structural Dynamics of the Vault Ribonucleoprotein Particle

Casañas A, Querol J. Fita I, Verdaguer N, M.A. Carrondo and P. Spadon (eds.)

Springer Science+Business Media B.V. (2012)

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Virus, el eslabón perdido entre organismos vivos y el mundo inerte. Libro: A través del cristal: como la cristalografía ha cambiado la visión del mundo.

Ferrer-Orta C, Querol-Audí J & Verdaguer N.

Colección Divulgación. CSIC, ISBN: 978-84-00-09800-1. (2014)

Project funding

Ongoing Projects

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PID2020-117976GB-I00 Title: “The role of protein-protein and protein-nucleic acid interactions in viral infection”. From September 1, 2021 to August 31, 2024

Amount € 278.300

Role: PI

Ministerio de Ciencia e Innovación

Proyecto PID2020-117976GB-I00 financiado por:

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PLEC2021-007654 Title: “Nueva inmunoterapia contra el cáncer: bloqueo de la reprogramación lipídica basada en el mapeo de transcriptomas de metástasis (LipIMMUNE)” . From November, 1, 2021 to October 31, 2024

Amount € 190.000

Role: PI

Ministerio de Ciencia e Innovación

Proyecto PLEC2021-007654 financiado por:

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Fundación “La Marató de TV3” Ref. 202136-30. Title: Towards understanding the molecular mechanisms of lethal mutagenesis in SARS-CoV-2. From July 30, 2021 to July 29, 2024

Amount € 150.000

Role: PI

“Fundació La Marató de TV3” Research Project, Edition 2021 –Research Projects in COVID-19

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CSIC Salud Gobal PTI+ Plataforma de Antivirales. Title: “Mutagénesis letal sinérgica para SARS-CoV-2 con muestras de virus de pacientes” From Jan 1, 2022 to December 31, 2022

Amount € 78200

Role: co-PI

CSIC

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Reference: 201833-10

Title: De l’estructura als mecanismes pels quals el virus Zika provoca neuropaties congènites

Total awarded: €160.000 (30.5.2019 – 30.12.2022)

Role: PI

“Fundació La Marató de TV3” Research Project, Edition 2017 – Biomedical Research Projects in Infectious Diseases

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Concluded Projects

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Reference: BIO2017-83906-P

Title: Bases estructurales de la infecion viral: Maquinarias replicativas de virus RNA

Total awarded: € 260.000 (1.1.2018 – 31.08.2022) Role: PI

Ministerio de Economía y Competitividad

Proyecto BIO2017-83906-P financiado por:

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Reference: MDM-2014-0435

Title: Appointment of the Department of Structural Biology of IBMB as a “María de Maeztu Unit of Excellence”

Total awarded: €2,000,000 (1.7.2015 – 31.12.2019)

Spanish Ministry of Economy and Competitivity.

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CSIC-COV-19-014. Title: “Combinaciones de antivirales frente a SARS-CoV-2”

From April 1, 2020 to December 31, 2021

Total awarded:  € 160.000

CSIC

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2020AEP121 Title: “Bases estructurales de la infección viral: interacción entre proteínas virales y proteínas del hospedador”. From Jan 1, 2020 to August 31, 2021

Total awarded:  € 43.262

CSIC

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