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Lab presentation

A unique feature of mitochondria is that they possess their own genome, the mitochondrial DNA (mtDNA), which codes for subunits of the electron transport chain that eventually leads to the synthesis of the ATP molecule. Dysregulation of this genome causes complex diseases and syndromes that are difficult to diagnose and treat. These are mostly classified as rare diseases. In the Structural MitoLab, we are interested in the structural basis underlying mtDNA regulation and packaging.

Another important line of research in our group are infectious diseases, which we approach by unveiling the mechanistic basis of the activity of proteins essential for organismal viability.

Our research is multidisciplinary and combines macromolecular X-ray crystallography with biochemical and biophysical analyses (chromatography, electrophoresis, SAXS, MALLS, etc.), which can be completed with additional techniques in collaboration with other groups.

Projects

Our group is interested in understanding the structural basis of mitochondrial genome regulation. In humans, the mtDNA is a circular molecule of 16.5kbp that codes for 13 essential subunits (out of approximately 80) of complexes I, III, IV and V of the oxidative phosphorylation pathway (OXPHOS), as well as for two rRNAs and 22tRNAs. The remaining OXPHOS subunits are imported from the cytosol. During mitochondrial fusion and fission, mtDNA is replicated and transmitted to daughter organelles. Therefore, correct transcription, replication and maintenance of the mtDNA are essential for cell viability.

Structural basis of mitochondrial DNA transcription and compaction. The mtDNA transcription initiation complex is formed by mitochondrial transcription factor A (TFAM) binding to one of the two mtDNA transcription promoters, HSP1 or LSP. At these promoters, TFAM recruits the RNA polymerase (mtRNAP). Factor B2, who binds mtRNAP, creates the replication bubble. We solved the crystal structure of TFAM bound to LSP. The protein encompasses two HMG-box domains, which are typically found in the nucleus. In TFAM, these domains insert residues into the DNA, disrupt the stacking between bases and induce a strong bend of 180º (Rubio-Cosials et al., 2011). In the complex, the protein and the DNA are intertwined, a binding mechanism that is possible by virtue of unliganded TFAM’s high flexibility and cooperativity between domains, as we showed by SAXS and FRET (Rubio-Cosials et al., 2011 and 2017). Two apparently homologous TFAM binding sites, DNA Site-X and Site-Y, similar to and downstream from LSP, unexpectedly show distinct DNA-structure features and TFAM binds to them in opposite directions, imposing again a U-turn (Cuppari el al., 2019). In these studies we showed that TFAM/DNA complexes multimerize at higher concentrations. Our biochemical analyses showed that TFAM binds to DNA structures, such as G-quadruplexes (Lyonnais et al., 2017).

All the data above posed the question whether a U-turn is the mtDNA compaction unit.

The U-turn was also found in the complex of S. cerevisiae mtDNA compacting protein Abf2p (Chakraborty et al., 2017). This protein also bears two HMG-boxes but the mechanism of binding is from one side of the DNA, as a staple. Therefore, the fact that evolutionary-distant eukaryotes show a similar U-turn suggested that this is the universal compaction unit, induced by different mechanisms.

Proteins involved in mtDNA replication. Other proteins studied in the laboratory and  whose structure we solved include single-strand binding protein mtSSB (or SSBP1, Piro-Mégy et al., 2020), the replicative helicase Twinkle (Fernández-Millán et al, 2015), and the transcription attenuator mTERF. Twinkle and mtSSB were, in addition of being observed in mitochondria, found in the RNE granules that lay close to the mtDNA (Hensen et al., 2019)

Proteins from pathogens, the way to a cure:

The laboratory is interested in the determination of the structure of proteins important for pathogen viability and virulence. This includes the peptidylarginine deiminase PPAD from the widespread odontopathogen Porphyromonas gingivalis. PPAD deiminates the guanidinium group of arginine, leading to excessive citrullination thereby causing inflammation. PPAD was solved with a general PAD inhibitory molecule at the active site. Furthermore, we also participated in the structure of a peptidase and sortase PorU, which processes virulent factors that are translocated by the T9 secretion system through the outer membrane. The results showed that PorU latency is in the form of a dimer while the active form as a monomer.

Lab people

The laboratory is headed by Dr. Maria Solà. After a tenure-tracked period of four years funded by a Ramón y Cajal contract, Maria Solà was awarded a permanent position as tenured Assistant Professor at IBMB-CSIC in 2008 and promoted to Associate Professor in 2019.

The research of the group, dedicated to proteins of biomedical interest, including proteins essential for mitochondrial or pathogen viability, involves post-doctoral fellows, PhD candidates and master students. National and international collaborations provide interdisciplinarity and give an expanded vision in the analysis of the proteins of interest.

Maria Solà also participates in teaching at courses and in scientific dissemination events.

ORCID: ORCID 0000-0002-0838-9706

Projects:

R&D project, Societal Challenges State Plan, Life Sciences Subplan, Ministry of Science, Innovation and Universities. “Structural analysis of proteins essential for mitochondria and pathogen viability”. Ref.: RTI2018-101015-B-100. Role: PI. 1.1.2019-31.08.2022.

Past students

Selected publications

Mizgalska, D., Goulas, T, Rodríguez-Banqueri, A., Veillarda, F., Madej, M., Małeckaa,  E., Szczesniaka, K., Ksiazeka. M., Widziołeka, M., Guevara, T., Eckhardb, U., Solà, M.*, Potempa,J.*, Gomis-Rüth, F.-X.* (2021). Intermolecular latency regulates the essential C-terminal signal peptidase and sortase of the Porphyromonas gingivalis type-IX secretion system. PNAS 2021 Vol. 118 No. 40 e2103573118.


Piro-Mégy, C., Sarzi, E., Tarrés-Solé, A., Péquignot, M., Hensen, F., Quilès, M., Manes, G., Sénéchal, A., Bocquet, B., Cazevieille, C., Roubertie, A., Müller, A., Charif, M., Goudenège, D., Lenaers, G., Wilhelm, H., Kellner, U., Weisschuh, N., Wissinger, B., Zanlonghi, X., Spelbrink* J.N., Sola, M.*, Delettre, C.* (2020). Dominant mutations in SSBP1 impair mtDNA replication and cause optic atrophy and foveopathy. Journal of Clinical Investigation, 130(1):143-156. DOI: 10.1172/JCI128513.


Cuppari, A., Fernández-Millán, P., Battistini, F., Tarrés-Solé, A., Lyonnais, S., Iruela, G., Ruiz-López, E., Enciso, Y., Rubio-Cosials, A., Prohens, R., Pons, M., Alfonso, C., Tóth, K., Rivas, G., Orozco, M., Solà, M. * (2019) DNA specificities modulate the binding of human transcription factor A to mitochondrial DNA control region. Nucleic Acids Research, 47: 6519–6537. DOI: 10.1093/nar/gkz406.

  • Selected as “Article of the Month” in the July 2019 issue of the Journal of the Spanish Society of Biophysics (SEB), Biofísica.

Picchioni, D., Antolin-Fontes, A., Camacho, N., Schmitz, C., Pons-Pons, A., Rodriguez-Escribà, M., Machallekidou, Güller, M.N., Siatra, P., A., Carretero-Junquera, M., Serrano, A., Hovde, S.-L., Knobel, P.A., Novoa E., Solà-Vilarrubias, M., Kaguni, L.S., Stracker, T.H., Ribas de Pouplana, L. (2019) Mitochondrial Protein Synthesis and mtDNA Levels Coordinated through an Aminoacyl-tRNA Synthetase Subunit. Cell Reports, 271:40-47. DOI: 10.1016/j.celrep.2019.03.022.c


F. Hensen, A. Potter, S. Esvel, A. Tarrés-Solé, A. Chakraborty., M. Solà, J.N. Spelbrink* (2019) Mitochondrial RNA granules are critically dependent on mtDNA replication factors Twinkle and mtSSB. Nucleic Acids Research 47(7):3680-3698. DOI: 10.1093/nar/gkz047. IF= 11.147 (2018/2019).


Bereta, G., Goulas, T., Madej, M., Bielecka, E., Solà, M.*, Potempa, J.*, Gomis-Rüth, F.X.* (2019) Structure, function and inhibition of a genomic/clinical variant of Porphyromonas gingivalis peptidylarginine deiminase. Protein Science 28(3):478-486. DOI: 10.1002/pro.3571. IF = 2.400. DOI: 10.1002/pro.3571


Rubio-Cosials, A., Battistini, F., Gansen, A., Cuppari, A., Bernadó, P., Orozco, M., Langowski, J., Tóth, K * & M. Solà*. (2018) Protein flexibility and synergy of HMG domains underlie U-turn bending of DNA by TFAM in solution. Biophysical Journal 114 (10): 2386 – 2396. DOI: 10.1016/j.bpj.2017.11.3743.


Lyonnais, S*., Tarrés-Solé, A., Rubio-Cosials, A., Cuppari, A., Brito, R., Jaumot, J., Gargallo, R., Vilaseca, M., Silva, C., Granzhan, A., Teulade-Fichou, M.-P., Eritja, R. & Solà, M*. (2017) The human mitochondrial transcription factor A is a versatile G-quadruplex binding protein. Scientific Reports, 7:43992. DOI: 10.1038/srep43992.


Chakraborty, A., Lyonnais, S., Battistini, F., Hospital, A., Medici, G., Prohens, R., Orozco, M., Vilardell, J. & Solà, M*. (2017) DNA structure directs positioning of the mitochondrial genome packaging protein Abf2p. Nucleic Acids Research, 45 (2): 951-967. DOI: 10.1093/nar/gkw1147. IF = 11.561.


Goulas, T., Mizgalska, D., Garcia-Ferrer, I., Kantyka, T., Guevara, T., Szmigielski, B., Sroka, A., Millan, C., Uson, I., Veillard, F., Potempa, B., Mydel, P., Solà, M.*, Potempa, J.* & Gomis-Ruth, F.X.* (2015). Structure and mechanism of a bacterial host-protein citrullinating virulence factor, Porphyromonas gingivalis peptidylarginine deiminase. Scientific Reports 5: 11969. DOI:10.1038/srep11969.


Fernández-Millán, P., Lázaro, M., Cansiz-Arda, S., Gerhold, J. M., Rajala, N., Schmitz, C.A., Silva-Espiña, C., Gil, D., Bernadó, P., Valle, M.*, Spelbrink, J.N.* & Solà, M* (2015). The hexameric structure of the human mitochondrial replicative helicase Twinkle. Nucleic Acids Research 43: 4284-4295. DOI:10.1093/nar/gkv189.


Rubio-Cosials, A. & Solà, M.* (2013). U-turn DNA bending by human mitochondrial transcription factor A. Current Opinion of Structural Biology 23: 116-124. DOI:10.1016/j.sbi.2012.12.004.


Rubio-Cosials, A., Sydow, J.F., Jiménez-Menéndez, N., Fernández-Millán, P., Montoya, J., Jacobs, H.T., Coll, M., Bernadó, P. &Solà, M.* (2011). Human mitochondrial transcription factor A induces a U-turn structure in the light strand promoter. Nature Structural and Molecular Biology 18: 1281–1289. DOI:10.1038/nsmb.2160.

  • Selected as “Article of the Month” in the December 2011 issue of the Journal of the Spanish Society of Biochemistry and Molecular Biology (SEBBM).
  • First author (from the Structural MitoLab) was awarded the 2nd Prize (Accésit) “Fischer Scientific” to a Young Investigator at the XXXV SEBBM Meeting, held in Sevilla (Spain) in September 2012.
  • Article mentioned in News and Views (Nature Structural and Molecular Biology 18: 1179–1181 (2011), DOI:10.1038/nsmb.2167).
  • Extraordinary PhD Award granted by the Doctorate School of the University of Barcelona.

Blanco, A.G., Canals, A., Bernués, J., Solà, M.& Coll, M. (2011). The structure of a transcription activation sub-complex reveals how σ70 is recruited to PhoB promoters. EMBO Journal 30: 3776 -3785. DOI:10.1038/emboj.2011.271.


Costenaro, L., Kaczmarska, Z., Arnan, C., Janowski, R., Coutard, B., Solà, M., Gorbalenya, A.E.; Norder, H.; Canard, B. & Coll, M. (2011). Structural basis for antiviral inhibition of the main protease, 3C, from human enterovirus 93. Journal of Virology 85: 10764-73. DOI:10.1128/JVI.05062-11.


Nadal, M., Mas, P., Blanco, A.G., Arnan, C., Solà, M., Hart, D. & Coll, M. (2010). Structure and inhibition of herpesvirus DNA packaging terminase nuclease domain.  Proceedings of the National Academy of Sciences USA 107: 16078-83. DOI:10.1073/pnas.1007144107.


Jiménez-Menéndez, N., Fernández-Millán, P., Rubio-Cosials, A., Arnan, C., Montoya, J., Jacobs, H.T., Bernadó, P., Coll, M., Usón, I. & Solà, M.* (2010). Human mitochondrial mTERF wraps around DNA through a left-handed superhelical tandem repeat. Nature Structural and Molecular Biology 17: 891-3. DOI:10.1038/nsmb.1859.

  • Selected as “Article of the Month” in the issue August 2010 of the Journal of the Spanish Society of Biochemistry and Molecular Biology (SEBBM).
  • First author (from the Structural MitoLab) was awarded the “José Tormo” Prize to a Young Investigator at the XXXIV SEBBM Meeting, held in Barcelona (Spain) in September 2011.

All publications

Mizgalska, D., Goulas, T, Rodríguez-Banqueri, A., Veillarda, F., Madej, M., Małeckaa,  E., Szczesniaka, K., Ksiazeka. M., Widziołeka, M., Guevara, T., Eckhardb, U., Solà, M.*, Potempa,J.*, Gomis-Rüth, F.-X.* (2021). Intermolecular latency regulates the essential C-terminal signal peptidase and sortase of the Porphyromonas gingivalis type-IX secretion system. PNAS 2021 Vol. 118 No. 40 e2103573118.


Piro-Mégy, C., Sarzi, E., Tarrés-Solé, A., Péquignot, M., Hensen, F., Quilès, M., Manes, G., Sénéchal, A., Bocquet, B., Cazevieille, C., Roubertie, A., Müller, A., Charif, M., Goudenège, D., Lenaers, G., Wilhelm, H., Kellner, U., Weisschuh, N., Wissinger, B., Zanlonghi, X., Spelbrink* J.N., Sola, M.*, Delettre, C.* (2020). Dominant mutations in SSBP1 impair mtDNA replication and cause optic atrophy and foveopathy. Journal of Clinical Investigation, 130(1):143-156. DOI: 10.1172/JCI128513. IF (2019) 11.864.


Cuppari, A., Fernández-Millán, P., Battistini, F., Tarrés-Solé, A., Lyonnais, S., Iruela, G., Ruiz-López, E., Enciso, Y., Rubio-Cosials, A., Prohens, R., Pons, M., Alfonso, C., Tóth, K., Rivas, G., Orozco, M., Solà, M. * (2019) DNA specificities modulate the binding of human transcription factor A to mitochondrial DNA control region. Nucleic Acids Research, 47: 6519–6537. DOI: 10.1093/nar/gkz406. IF (2018/2019) = 11.147.

  • Selected as “Article of the Month” in the July 2019 issue of the Journal of the Spanish Society of Biophysics (SEB), Biofísica.

Picchioni, D., Antolin-Fontes, A., Camacho, N., Schmitz, C., Pons-Pons, A., Rodriguez-Escribà, M., Machallekidou, Güller, M.N., Siatra, P., A., Carretero-Junquera, M., Serrano, A., Hovde, S.-L., Knobel, P.A., Novoa E., Solà-Vilarrubias, M., Kaguni, L.S., Stracker, T.H., Ribas de Pouplana, L. (2019) Mitochondrial Protein Synthesis and mtDNA Levels Coordinated through an Aminoacyl-tRNA Synthetase Subunit. Cell Reports, 271:40-47. DOI: 10.1016/j.celrep.2019.03.022.c IF (in 2018/2019) = 7.815


F. Hensen, A. Potter, S. Esvel, A. Tarrés-Solé, A. Chakraborty., M. Solà, J.N. Spelbrink* (2019) Mitochondrial RNA granules are critically dependent on mtDNA replication factors Twinkle and mtSSB. Nucleic Acids Research 47(7):3680-3698. DOI: 10.1093/nar/gkz047. IF= 11.147 (2018/2019).


Bereta, G., Goulas, T., Madej, M., Bielecka, E., Solà, M.*, Potempa, J.*, Gomis-Rüth, F.X.* (2019) Structure, function and inhibition of a genomic/clinical variant of Porphyromonas gingivalis peptidylarginine deiminase. Protein Science 28(3):478-486. DOI: 10.1002/pro.3571. IF = 2.400. DOI: 10.1002/pro.3571


Rubio-Cosials, A., Battistini, F., Gansen, A., Cuppari, A., Bernadó, P., Orozco, M., Langowski, J., Tóth, K * & M. Solà*. (2018) Protein flexibility and synergy of HMG domains underlie U-turn bending of DNA by TFAM in solution. Biophysical Journal 114 (10): 2386 – 2396. DOI: 10.1016/j.bpj.2017.11.3743. IF = 3.665.


Lyonnais, S*., Tarrés-Solé, A., Rubio-Cosials, A., Cuppari, A., Brito, R., Jaumot, J., Gargallo, R., Vilaseca, M., Silva, C., Granzhan, A., Teulade-Fichou, M.-P., Eritja, R. & Solà, M*. (2017) The human mitochondrial transcription factor A is a versatile G-quadruplex binding protein. Scientific Reports, 7:43992. DOI: 10.1038/srep43992. IF = 4.122.


Chakraborty, A., Lyonnais, S., Battistini, F., Hospital, A., Medici, G., Prohens, R., Orozco, M., Vilardell, J. & Solà, M*. (2017) DNA structure directs positioning of the mitochondrial genome packaging protein Abf2p. Nucleic Acids Research, 45 (2): 951-967. DOI: 10.1093/nar/gkw1147. IF = 11.561.


Goulas, T., Mizgalska, D., Garcia-Ferrer, I., Kantyka, T., Guevara, T., Szmigielski, B., Sroka, A., Millan, C., Uson, I., Veillard, F., Potempa, B., Mydel, P., Solà, M.*, Potempa, J.* & Gomis-Ruth, F.X.* (2015). Structure and mechanism of a bacterial host-protein citrullinating virulence factor, Porphyromonas gingivalis peptidylarginine deiminase. Scientific Reports 5: 11969. DOI:10.1038/srep11969.


Fernández-Millán, P., Lázaro, M., Cansiz-Arda, S., Gerhold, J. M., Rajala, N., Schmitz, C.A., Silva-Espiña, C., Gil, D., Bernadó, P., Valle, M.*, Spelbrink, J.N.* & Solà, M* (2015). The hexameric structure of the human mitochondrial replicative helicase Twinkle. Nucleic Acids Research 43: 4284-4295. DOI:10.1093/nar/gkv189.


Litwin, T., Solà, M., Holt, I., Neuman., K* (2015) A robust assay to measure DNA topology-dependent protein binding affinity. Nucleic Acids Research 43: e43 (Methods Online). DOI:10.1093/nar/gku1381.


Benabou, S., Ferreira, R., Aviñó, A., González, C., Lyonnais, S., Solà, M., Eritja, R., Jaumot, J., Gargallo, R. (2014). Solution equilibria of cytosine- and guanine-rich sequences near the promoter region of the n-myc gene that contain stable hairpins within lateral loops. Biochimica et Biophysica Acta – General Subjects 1840: 41-52. DOI:10.1016/j.bbagen.2013.08.028.


Trillo-Muyo, S., Jasilionis, A., Domagalski, M.J., Chruszcz, M., Minor, W., Kuisiene, N., Arolas, J.L., Solà, M., Gomis-Rüth, F.X.*  (2013). Ultratight crystal packing of a 10 kDa protein. Acta Crystallographica section D69: 464-470. DOI:10.1107/S0907444912050135.


Rubio-Cosials, A. & Solà, M.* (2013). U-turn DNA bending by human mitochondrial transcription factor A. Current Opinion of Structural Biology 23: 116-124. DOI:10.1016/j.sbi.2012.12.004.


Rubio-Cosials, A., Sydow, J.F., Jiménez-Menéndez, N., Fernández-Millán, P., Montoya, J., Jacobs, H.T., Coll, M., Bernadó, P. &Solà, M.* (2011). Human mitochondrial transcription factor A induces a U-turn structure in the light strand promoter. Nature Structural and Molecular Biology 18: 1281–1289. DOI:10.1038/nsmb.2160.

  • Selected as “Article of the Month” in the December 2011 issue of the Journal of the Spanish Society of Biochemistry and Molecular Biology (SEBBM).
  • First author (from the Structural MitoLab) was awarded the 2nd Prize (Accésit) “Fischer Scientific” to a Young Investigator at the XXXV SEBBM Meeting, held in Sevilla (Spain) in September 2012.
  • Article mentioned in News and Views (Nature Structural and Molecular Biology 18: 1179–1181 (2011), DOI:10.1038/nsmb.2167).
  • Extraordinary PhD Award granted by the Doctorate School of the University of Barcelona.

Blanco, A.G., Canals, A., Bernués, J., Solà, M.& Coll, M. (2011). The structure of a transcription activation sub-complex reveals how σ70 is recruited to PhoB promoters. EMBO Journal 30: 3776 -3785. DOI:10.1038/emboj.2011.271.


Costenaro, L., Kaczmarska, Z., Arnan, C., Janowski, R., Coutard, B., Solà, M., Gorbalenya, A.E.; Norder, H.; Canard, B. & Coll, M. (2011). Structural basis for antiviral inhibition of the main protease, 3C, from human enterovirus 93. Journal of Virology 85: 10764-73. DOI:10.1128/JVI.05062-11.


Norder, H., De Palma, A.M., Selisko, B., Costenaro, L., Papageorgiou, N., Arnan, C., Coutard, B., Lantez, V., De Lamballerie, X., Baronti, C., Solà, M., Tan, J., Neyts, J., Canard, B., Coll, M., Gorbalenya, A.E. & Hilgenfeld, R. (2011). Picornavirus non-structural proteins as targets for new anti-virals with broad activity. Antiviral Research 89: 204-18.DOI:10.1016/j.antiviral.2010.12.007.


Nadal, M., Mas, P., Blanco, A.G., Arnan, C., Solà, M., Hart, D. & Coll, M. (2010). Structure and inhibition of herpesvirus DNA packaging terminase nuclease domain.  Proceedings of the National Academy of Sciences USA 107: 16078-83. DOI:10.1073/pnas.1007144107.


Jiménez-Menéndez, N., Fernández-Millán, P., Rubio-Cosials, A., Arnan, C., Montoya, J., Jacobs, H.T., Bernadó, P., Coll, M., Usón, I. & Solà, M.* (2010). Human mitochondrial mTERF wraps around DNA through a left-handed superhelical tandem repeat. Nature Structural and Molecular Biology 17: 891-3. DOI:10.1038/nsmb.1859.

  • Selected as “Article of the Month” in the issue August 2010 of the Journal of the Spanish Society of Biochemistry and Molecular Biology (SEBBM).
  • First author (from the Structural MitoLab) was awarded the “José Tormo” Prize to a Young Investigator at the XXXIV SEBBM Meeting, held in Barcelona (Spain) in September 2011.

Monferrer, D., Tralau, T., Kertesz, M. A., Dix, I., Solà, M. & Usón, I. (2010). Structural studies on the full-length LysR-type regulator TsaR from Comamonas testosteroni T-2 reveal a novel open conformation of the tetrameric LTTR fold. Molecular Microbiology 75: 1199-1214. DOI:10.1111/j.1365-2958.2010.07043.x.


Wójtowicz H, Guevara T, Tallant C, Olczak M, Sroka A, Potempa J, Solà M, Olczak T, Gomis-Rüth FX. (2009). Unique structure and stability of HmuY, a novel heme-binding protein of Porphyromonas gingivalis. PLoS Pathogens 5: e1000419.DOI:10.1371/journal.ppat.1000419.


Niemirowicz,G.,  Fernández, D., Solà, M., Cazzulo, J.-J., Avilés, F.X. & Gomis-Rüth, F.X. (2008). The molecular analysis of Trypanosoma cruzi metallocarboxypeptidase 1 provides insight into fold and substrate specificity. Molecular Microbiology75: 853–866.DOI:10.1111/j.1365-2958.2008.06444.x.


Sanglas, L., Valnickova, Z., Arolas, J. L., Pallarés, I., Guevara, T., Solà, M., Kristensen, T., Enghild, J.J., Avilés, F.X. & Gomis-Rüth, F.X. (2008). Structure of activated thrombin-activatable fibrinolysis inhibitor, a molecular link between coagulation and fibrinolysis. Molecular Cell 31: 598-606. DOI:10.1016/j.molcel.2008.05.031.


Mallorquí-Fernández, N., Manandhar, S.P., Mallorquí-Fernández, G., Usón, I., Wawrzonek, K., Kantyka, T., Solà, M., Thøgersen, I. B., Enghild, J., Potempa, J. & Gomis-Rüth, F.X. (2008). A new autocatalytic activation mechanism for cysteine proteases revealed by Prevotella intermedia interpain A. Journal of Biological Chemistry 283: 2871-2882. DOI:10.1074/jbc.M708481200.


Tallant, C., García-Castellanos, R., Marrero, A., Canals, F., Yang, Y., Reymond, J.L., Solà, M., Baumann U. & Gomis-Rüth, F.X. (2007). Activity of ulilysin, an archaeal PAPP-A-related gelatinase and IGFBP-protease. Biological Chemistry 388: 1243-1253. DOI:10.1515/BC.2007.143.


Bayés, A., Fernandez, D., Solà, M., Marrero, A., Garcia-Piqué, S., Aviles, F.X., Vendrell, J. & Gomis-Rüth, F.X. (2007). Caught after the act: a human A-type metallocarboxypeptidase in a product complex with a cleaved hexapeptide. Biochemistry46: 6921-6930.DOI:10.1021/bi700480b¡¡


Saiyed, T., Paarman, I., Schmitt, B., Haeger, S., Solà, M., Schmalzing, G., Weissenhorn, W., &Betz, H. (2007). Molecular basis of gephyrin clustering at inhibitory synapses: role of G- and E domain interactions. Journal of Biological Chemistry 282: 5625-5632. DOI:10.1074/jbc.M610290200. Q1; IF =


Arribas-Bosacoma, R., Kim, S.-K., Ferrer-Orta, C., Blanco, A.G., Pereira, P.J.B., Gomis-Rüth, F. X., Wanner, B.L., Coll, M.  & Solà, M.* (2007). The X-ray crystal structures of two constitutively active mutants of the E. coli PhoB receiver domains gives insights into activation. Journal of Molecular Biology 366: 626-641. DOI:10.1016/j.jmb.2006.11.038.


García-Castellanos, R., Tallant, C., Solà, M., Baumann, U. & Gomis-Rüth, F.X. (2007). Substrate specificity of a metalloprotease of the pappalysin family revealed by an inhibitor and the product complexArchives in Biochemistry and Biophysics 457: 57-72. DOI:10.1016/j.abb.2006.10.004.


Solà, M.*, Drew, D.L., Blanco, A.G., Gomis-Rüth, F. X.& Coll, M. (2006). The co-factor induced pre-active conformation in PhoB. Acta Crystallographica section D62: 1046-1057. DOI:10.1107/S0907444906024541.


Guevara, T., Mallorquí-Fernández, N., García-Piqué, S., Petersen, G.E., Lauritzen, C., Pedersen, J., Arnau, J., Gomis-Rüth, F.X.  & Solà, M.* (2006). Papaya glutamine cyclotransferase shows singular fivefold beta-propeller architecture that suggests a novel reaction mechanism. Biological Chemistry 387: 1479 – 1486. DOI:10.1515/BC.2006.185.


Gomis-Rüth, F.X., Solà, M., de la Cruz, F. & Coll, M. (2004). Coupling factors in macromolecular type-IV secretion machineries. Current Pharmaceutical Design 10: 1551-1565. DOI:10.2174/1381612043384817.


Solà, M., Bavro, V.N., Timmins, J., Franz, T., Ricard-Blum, S., Schoen, G., Ruigrok, R.W.H., Paarman, I., Saiyed, T., O’Sullivan, G., Schmitt, G., Betz, H. & Weissenhorn, W. (2004). Structural basis of dynamic glycine receptor clustering by gephyrin. EMBO Journal 23: 2510-2519. DOI:10.1038/sj.emboj.7600256.


Blanco, A.G., Sola, M., Gomis-Rüth, F.X. & Coll, M.(2002). Tandem DNA recognition by PhoB, a two-component signal transduction transcriptional activator. Structure10: 61-73. DOI:10.1016/S0969-2126(02)00761-X.


Bavro, V.N., Sola, M., Bracher, A., Kneussel, M., Betz, H. & Weissenhorn, W. (2002). Crystal structure of the GABAA -receptor-associated protein GABARAP. EMBO Reports 3: 183-189. DOI:10.1093/embo-reports/kvf026.


Costa, M., Solà, M., del Solar, G., Eritja, R., Hernández-Arriaga, A.M., Espinosa, M., Gomis-Rüth, F.X. & Coll, M. (2001). Plasmid transcriptional repressor CopG oligomerises to render helical superstructures unbound and in complexes with oligonucleotides.  Journal of Molecular Biology 310: 403-417. DOI:10.1006/jmbi.2001.4760.


Solà, M., Kneussel, M., Heck, I.S., Betz, H. & Weissenhorn, W. (2001) X-ray crystal structure of the trimeric N-terminal domain of Gephyrin. Journal of Biological Chemistry 276: 25294-25301. DOI:10.1074/jbc.M101923200.


Solà, M., López Hernández, E., Cronet, P., Lacroix, E., Serrano, L., Coll, M., & Párraga, A. (2000). Towards understanding a molecular switch mechanism: thermodynamic and crystallographic studies of the signal transduction protein CheY.Journal of Molecular Biology 303: 213-225. DOI:10.1006/jmbi.2000.4507.


González, A., Pédélac, J.D., Solà, M., Gomis–Rüth, F.X., Coll, M., Samama, J.P. & Benini, S. (1999). Two-wavelength MAD phasing: in search of the optimal choice of wavelengths. Acta Crystallographica section D55: 1449-1458. DOI:10.1107/S0907444999006745.


Solà, M., Gomis–Rüth, F.X., Serrano, L., González, A., & Coll, M. (1999). Three-dimensional crystal structure of the transcription factor PhoB receiver domain. Journal of Molecular Biology85: 675-687. DOI:10.1006/jmbi.1998.2326.


Solà, M., Gomis–Rüth, F.X., Guasch, A., Serrano, L. & Coll, M. (1998). Overexpression, purification, crystallization and preliminary X-ray diffraction analysis of the receiver domain of PhoB. Acta Crystallographica section D54: 1460-1463. DOI:10.1107/S0907444998006143.


Gomis–Rüth, F.X., Solà, M., Pérez-Luque, R., Acebo, P., Alda, M. T., González, A., Espinosa, M., del Solar G. & Coll M. (1998). Overexpression, purification, crystallization and preliminary X-ray diffraction analysis of the pMV158-encoded plasmid transcriptional repressor protein CopG.FEBS letters 425: 161-165. DOI:10.1016/S0014-5793(98)00219-1.


Gomis–Rüth, F.X., Solà, M., Acebo, P., Párraga, A., González, A., Eritja, R., Espinosa, M., del Solar, G., & Coll, M. (1998). The structure of the plasmid-encoded transcriptional repressor CopG, unliganded and bound to its operator.EMBO Journal 17: 7404-7415. DOI:10.1093/emboj/17.24.7404.

Project Funding

Ongoing Projects


Reference: RTI2018-101015-B-100 (01.01.2019 – 31.08.2022)

Title: Structural analysis of proteins essential for mitochondria and pathogen viability

R&D project, Societal Challenges State Plan, Life Sciences Subplan, Ministry of Science, Innovation and Universities.


Concluded Projects


Reference: 2017 SGR 1192 (01.01.2017 – 31.12.2019)

Title: Computational methods and structure-function studies of proteins involved in mitochondrial pathologies and from pathogenic microorganisms (PATHOMET)

Consolidated Research Groups of Catalunya Grant, Generalitat of Catalunya.


Reference: BFU2015-70645-R

Title: Structural analysis of the mitocondrial genome and its regulation

R&Dproject, Fundamental Biology Plan, Molecular and Cellular Biology Subplan, Ministry of Economy and Competitiveness


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.


Reference: FP7-HEALTH-2012-306029-2 “TRIGGER”

Title: King of hearts, joints and lungs; periodontal pathogens as etiologic factor in RA, CVD and COPD and their impact on treatment strategies

(1.4.2013 – 31.3.2017)

European Union STREP FP7 Project


Reference: FP7-PEOPLE-2011-290246 “RAPID”

Title: RAPID-Rheumatoid arthritis and periodontal inflammatory disease

Coordinator: Thomas Dietrich (Birmingham, UK). WP nº 3

(1.4.2012 – 31.3.2016)

European Union Marie Curie Initial Training Network (ITN) Project


Reference: BFU2012-33516/BMC

Title: Structural Basis of Mitochondrial Genome Regulation

(1.1.2013-31.12.2015)

R&Dproject, Fundamental Biology Plan, Molecular and Cellular Biology Subplan, Ministry of Economy and Competitiveness.


Reference: FP7-HEALTH-2010-261460

Title: Protein citrullination as a link between periodontal diseases and rheumatoid arthritis (RA) and target for development of novel drugs to treat RA

(1.11.2010 – 31.10.2014)

Coordinator: Peter Mydel (Göteborg, Sweden). WP nº 3

European Union STREP FP7 Project


Reference: BFU2009-07134/BMC

Title: Structural Biology of Mitochondrial Genome Regulation

(1.1.2010-31.12.2012)

Coordinator: Peter Mydel (Göteborg, Sweden). WP nº 3

R&Dproject, Fundamental Biology Plan, Molecular, Cellular and Genetics Biology Subplan, Ministry of Science and Innovation.


Reference: BFU2006-09593/BMC

R&D project, Fundamental Biology Plan, Molecular and Cellular Biology Subplan financed by the Ministry of Education and Science.


Reference: PIE 200820I045

C.S.I.C “Intramural” Project.


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