Structural bioinformatics and molecular modelling

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We use bioinformatics and theoretical structural biology methods to understand the principles of protein structure and biomolecular interactions. Today, bioinformatics plays an increasingly important role in biological research. The mass of genome sequencing data significantly exceeds the development of our data analysis capacity. The dramatic growth of genomic data presents new challenges for scientists. Indeed, making sense of millions of protein sequences requires systematic approaches and information about their 3D structure as well as their evolutionary and functional relationships. In line with this tendency, we focus on developing bioinformatics tools for the large-scale, structural and functional annotation of proteomes.

We are particularly interested in:

Proteins with tandem repeats

We pioneered the bioinformatics analysis, classification, structural prediction and modelling of proteins with repeats that fold into a solenoid-like arrangement. Further development of reliable methods for the identification of repetitive protein motifs and the ab initio prediction of their 3D structures promises to be a fertile research field in structural bioinformatics. Over the last years, many evidences have been accumulated about the high incidence of tandem repeats in the amino acid sequences of virulence factors of pathogens and of some amyloidogenic proteins and prions. Thus, the discovery and structure-function predictions of these domains could lead to the identification of targets for new drugs and vaccines against emerging infectious diseases and to the development of amyloidogenesis inhibitors.

Amyloid and Prions

Several lines of evidence suggest that amyloid fibrils play a causative role in several neurodegenerative diseases, including Alzheimer’s, Parkinson’s and Huntington’s disease. The determination of the fibril structure goes through the prediction of structural models based on the accumulated experimental evidences, until a unique model can explain the whole set of data. We are contributing to this progress by developing structural models for the amyloid and prion fibrils. Our ultimate goals are the structure-based prediction of the amyloidogenic properties of amino acid sequences and the rational design of fibrillogenesis inhibitors.

Contact our team

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Andrey Kajava

Members of the team

  • Marie-Therese CHATEAU
    (Staff Scientist) +33 (0)4 34 35 95 39
  • Theo FALGARONE
    (PhD Student) +33 (0)4 34 35 95 39
  • Andrey KAJAVA Group Leader
    (Staff Scientist) +33 (0)4 34 35 95 38
  • Etienne VILLAIN
    (PhD Student) +33 (0)4 34 35 95 39
    • 2019

      The HslV Protease from Leishmania major and Its Activation by C-terminal HslU Peptides.

      Kebe NM, Samanta K, Singh P, Lai-Kee-Him J, Apicella V, Payrot N, Lauraire N, Legrand B, Lisowski V, Mbang-Benet D,[...]

      Int J Mol Sci. 20(5). Pubmed

    • 2018

      Porins and Amyloids are Coded by Similar Sequence Motifs.

      Villain E, Nikekhin AA, Kajava AV.

      Proteomics. e1800075. Pubmed

    • 2018

      Post-Translational Modifications and Diastolic Calcium Leak Associated to the Novel RyR2-D3638A Mutation Lead to CPVT in Patient-Specific hiPSC-Derived Cardiomyocytes.

      Acimovic I, Refaat MM, Moreau A, Salykin A, Reiken S, Sleiman Y, Souidi M, Přibyl J, Kajava AV, Richard S,[...]

      J Clin Med. 8;7(11). Pubmed

    • 2018

      Protein Co-Aggregation Related to Amyloids: Methods of Investigation, Diversity, and Classification.

      Bondarev SA, Antonets KS, Kajava AV, Nizhnikov AA, Zhouravleva GA.

      Int J Mol Sci. ; 19(8) Pubmed

    • 2018

      BetaSerpentine: a bioinformatics tool for reconstruction of amyloid structures.

      Bondarev SA, Bondareva OV, Zhouravleva GA, Kajava AV.

      Bioinformatics. 34(4):599-608 Pubmed

    • 2018

      Editorial for special issue “Proteins with tandem repeats: sequences, structures and functions”.

      Kajava AV, Tosatto SCE.

      J Struct Biol. 201(2):86-87. Pubmed

    • 2018

      Identification of the Autochaperone Domain in the Type Va Secretion System (T5aSS): Prevalent Feature of Autotransporters with a β-Helical Passenger.

      Rojas-Lopez M, Zorgani MA, Kelley LA, Bailly X, Kajava AV, Henderson IR, Polticelli F, Pizza M, Rosini R, Desvaux M.

      Front Microbiol. 8:2607. Pubmed

    • 2018

      Establishment of Constraints on Amyloid Formation Imposed by Steric Exclusion of Globular Domains.

      Azizyan RA, Garro A, Radkova Z, Anikeenko A, Bakulina A, Dumas C, Kajava AV.

      J Mol Biol. 430(20):3835-3846. Pubmed

    • 2017

      Classification of β-hairpin repeat proteins.

      Roche DB, Viet PD, Bakulina A, Hirsh L, Tosatto SCE, Kajava AV.

      J Struct Biol. pii: S1047-8477(17)30162-4. Pubmed

    • 2017

      Usage of a dataset of NMR resolved protein structures to test aggregation versus solubility prediction algorithms.

      Roche DB, Villain E, Kajava AV.

      Protein Sci. 26(9):1864-1869. Pubmed

    • 2017

      DisProt 7.0: a major update of the database of disordered proteins.

      Piovesan D, Tabaro F, Mičetić I, Necci M, Quaglia F, Oldfield CJ, Aspromonte MC, Davey NE, Davidović R, Dosztányi Z,[...]

      Nucleic Acids Res. 45:D219-D227. Pubmed

    • 2017

      RepeatsDB 2.0: improved annotation, classification, search and visualization of repeat protein structures.

      Paladin L, Hirsh L, Piovesan D, Andrade-Navarro MA, Kajava AV, Tosatto SC.

      Nucleic Acids Res. 45:D308-D312. Pubmed

    • 2016

      Functional assignment to positively selected sites in the core type III effector RipG7 from Ralstonia solanacearum.

      Wang K, Remigi P, Anisimova M, Lonjon F, Kars I, Kajava A, Li CH, Cheng CP, Vailleau F, Genin S,[...]

      Mol Plant Pathol. 17(4):553-64. Pubmed

    • 2016

      Global genetic diversity of the Plasmodium vivax transmission-blocking vaccine candidate Pvs48/45.

      Vallejo AF, Martinez NL, Tobon A, Alger J, Lacerda MV, Kajava AV, Arévalo-Herrera M, Herrera S.

      Malar J. 15:202. Pubmed

    • 2016

      Tally: a scoring tool for boundary determination between repetitive and non-repetitive protein sequences.

      Richard FD, Alves R, Kajava AV.

      Bioinformatics. 32:1952-8. Pubmed

    • 2016

      α-Synuclein Amyloid Fibrils with Two Entwined, Asymmetrically Associated Protofibrils.

      Dearborn AD, Wall JS, Cheng N, Heymann JB, Kajava AV, Varkey J, Langen R, Steven AC.

      J Biol Chem. 291:2310-8. Pubmed

    • 2015

      In search of the boundary between repetitive and non-repetitive protein sequences.

      Richard FD, Kajava AV.

      Biochem Soc Trans. 43:807-11. Pubmed

    • 2015

      Restricted mobility of side chains on concave surfaces of solenoid proteins may impart heightened potential for intermolecular interactions.

      Ramya L, Gautham N, Chaloin L, Kajava AV.

      Proteins. 83:1654-64. Pubmed

    • 2015

      Single substitution in bacteriophage T4 RNase H alters the ratio between its exo- and endonuclease activities.

      Kholod N, Sivogrivov D, Latypov O, Mayorov S, Kuznitsyn R, Kajava AV, Shlyapnikov M, Granovsky I.

      Mutat Res. 781:49-57. Pubmed

    • 2015

      Evolution of proteasome regulators in eukaryotes.

      Fort P, Kajava AV, Delsuc F, Coux O.

      Genome Biol Evol. 7:1363-79. Pubmed

    • 2015

      TAPO: A combined method for the identification of tandem repeats in protein structures.

      Do Viet P, Roche DB, Kajava AV.

      FEBS Lett. 589:2611-9. Pubmed

    • 2015

      Structure-based view on [PSI(+)] prion properties.

      Bondarev SA, Zhouravleva GA, Belousov MV, Kajava AV.

      Prion. 9:190-9. Pubmed

    • 2015

      Designs on a curve.

      Bazan JF, Kajava AV.

      Nat Struct Mol Biol. 22:103-5. Pubmed

    • 2015

      A structure-based approach to predict predisposition to amyloidosis.

      Ahmed AB, Znassi N, Château MT, Kajava AV.

      Alzheimers Dement. 11:681-90. Pubmed

    • 2014

      TRDistiller: a rapid filter for enrichment of sequence datasets with proteins containing tandem repeats.

      Richard FD, Kajava AV.

      J Struct Biol. 186:386-91. Pubmed

    • 2014

      Evolutionary link between metazoan RHIM motif and prion-forming domain of fungal heterokaryon incompatibility factor HET-s/HET-s.

      Kajava AV, Klopffleisch K, Chen S, Hofmann K.

      Sci Rep. 4:7436. Pubmed

    • 2014

      Conformational switching in PolyGln amyloid fibrils resulting from a single amino acid insertion.

      Huang RK1 Baxa U, Aldrian G, Ahmed AB, Wall JS, Mizuno N, Antzutkin O, Steven AC, Kajava AV.

      Biophys J. 106:2134-42. Pubmed

    • 2014

      RepeatsDB: a database of tandem repeat protein structures.

      Di Domenico T, Potenza E, Walsh I, Parra RG, Giollo M, Minervini G, Piovesan D, Ihsan A, Ferrari C, Kajava[...]

      Nucleic Acids Res. 42:D352-7. Pubmed

    • 2014

      Plasmodium vivax antigen discovery based on alpha-helical coiled coil protein motif.

      Céspedes N, Habel C, Lopez-Perez M, Castellanos A, Kajava AV, Servis C, Felger I, Moret R, Arévalo-Herrera M, Corradin G,[...]

      PLoS One. 9:e100440. Pubmed

    • 2014

      Drosophila Spag is the homolog of RNA polymerase II-associated protein 3 (RPAP3) and recruits the heat shock proteins 70 and 90 (Hsp70 and Hsp90) during the assembly of cellular machineries.

      Benbahouche Nel H, Iliopoulos I, Török I, Marhold J, Henri J, Kajava AV, Farkaš R, Kempf T, Schnölzer M, Meyer[...]

      J Biol Chem. 289:6236-47. Pubmed

    • 2014

      Plasmodium falciparum merozoite surface protein 2: epitope mapping and fine specificity of human antibody response against non-polymorphic domains.

      Balam S, Olugbile S, Servis C, Diakité M, D'Alessandro A, Frank G, Moret R, Nebie I, Tanner M, Felger I,[...]

      Malar J. 13:510. Pubmed

    • 2014

      A structure-based approach to predict predisposition to amyloidosis.

      Ahmed AB, Znassi N, Château MT, Kajava AV.

      Alzheimers Dement. 11:681-90. Pubmed

    • 2013

      Breaking the amyloidogenicity code: methods to predict amyloids from amino acid sequence.

      Ahmed AB, Kajava AV.

      FEBS Lett. 587(8):1089-95. Pubmed

    • 2013

      Antigenicity and immunogenicity of a novel chimeric peptide antigen based on the P. vivax circumsporozoite protein.

      Céspedes N, Arévalo-Herrera M, Felger I, Reed S, Kajava AV, Corradin G, Herrera S.

      Vaccine. 31(42):4923-30. Pubmed

    • 2013

      Effect of charged residues in the N-domain of Sup35 protein on prion [PSI+] stability and propagation.

      Bondarev SA, Shchepachev VV, Kajava AV, Zhouravleva GA.

      J Biol Chem. 288(40):28503-13. Pubmed

    • 2013

      EpCAM controls actomyosin contractility and cell adhesion by direct inhibition of PKC.

      Maghzal N, Kayali HA, Rohani N, Kajava AV, Fagotto F.

      Dev Cell. 27(3):263-77. Pubmed

    • 2012

      Tandem repeats in proteins: from sequence to structure.

      Kajava AV.

      J Struct Biol. 179(3):279-88. Pubmed

    • 2012

      Malaria vaccine development using synthetic peptides as a technical platform.

      Corradin G, Céspedes N, Verdini A, Kajava AV, Arévalo-Herrera M, Herrera S.

      Adv Immunol. 114:107-49. Pubmed

    • 2012

      PRDB: Protein Repeat DataBase.

      Jorda J, Baudrand T, Kajava AV.

      Proteomics. 12(9):1333-6. Pubmed

    • 2012

      Repeat or not repeat?–Statistical validation of tandem repeat prediction in genomic sequences.

      Schaper E, Kajava AV, Hauser A, Anisimova M.

      Nucleic Acids Res. 40(20):10005-17. Pubmed

    • 2012

      Cell biological characterization of the malaria vaccine candidate trophozoite exported protein 1.

      Kulangara C, Luedin S, Dietz O, Rusch S, Frank G, Mueller D, Moser M, Kajava AV, Corradin G, Beck HP,[...]

      PLoS One. 7(10):e46112. Pubmed

    • 2011

      Identification of residues within tropomodulin-1 responsible for its localization at the pointed ends of the actin filaments in cardiac myocytes.

      Tsukada T, Kotlyanskaya L, Huynh R, Desai B, Novak SM, Kajava AV, Gregorio CC, Kostyukova AS.

      J Biol Chem. 286(3):2194-204. Pubmed

    • 2011

      Malaria vaccine candidate: design of a multivalent subunit α-helical coiled coil poly-epitope.

      Olugbile S, Villard V, Bertholet S, Jafarshad A, Kulangara C, Roussilhon C, Frank G, Agak GW, Felger I, Nebie I,[...]

      Vaccine. 29(40):7090-9. Pubmed

    • 2010

      A network of hydrogen bonds on the surface of TLR2 controls ligand positioning and cell signaling.

      Kajava AV, Vasselon T.

      J Biol Chem. 2010 285(9):6227-34. Pubmed

    • 2010

      Beta arcades: recurring motifs in naturally occurring and disease-related amyloid fibrils.

      Kajava AV, Baxa U, Steven AC.

      FASEB J. 24(5):1311-9. Pubmed

    • 2010

      Malaria vaccine: why is it taking so long?

      Corradin G, Kajava AV.

      Expert Rev Vaccines. 9(2):111-4. Pubmed

    • 2010

      Protein tandem repeats – the more perfect, the less structured.

      Jorda J, Xue B, Uversky VN, Kajava AV.

      FEBS J. 277(12):2673-82. Pubmed

    • 2010

      Structural basis for the wobbler mouse neurodegenerative disorder caused by mutation in the Vps54 subunit of the GARP complex.

      Pérez-Victoria FJ, Abascal-Palacios G, Tascón I, Kajava A, Magadán JG, Pioro EP, Bonifacino JS, Hierro A.

      Proc Natl Acad Sci U S A. 107(29):12860-5. Pubmed

    • 2010

      Protein homorepeats sequences, structures, evolution, and functions.

      Jorda J, Kajava AV.

      Adv Protein Chem Struct Biol. 79:59-88. Pubmed

    • 2010

      Long synthetic peptides for the production of vaccines and drugs: a technological platform coming of age.

      Corradin G, Kajava AV, Verdini A.

      Sci Transl Med. 2(50):50rv3. Pubmed

    • 2009

      The C-terminal domain of Plasmodium falciparum merozoite surface protein 3 self-assembles into alpha-helical coiled coil tetramer.

      Gondeau C, Corradin G, Heitz F, Le Peuch C, Balbo A, Schuck P, Kajava AV.

      Mol Biochem Parasitol. 165(2):153-61. Pubmed

    • 2009

      Sequence conservation in Plasmodium falciparum alpha-helical coiled coil domains proposed for vaccine development.

      Kulangara C, Kajava AV, Corradin G, Felger I.

      PLoS One. 4(5):e5419. Pubmed

    • 2009

      T-REKS: identification of Tandem REpeats in sequences with a K-meanS based algorithm.

      Jorda J, Kajava AV.

      Bioinformatics. 25(20):2632-8. Pubmed

    • 2009

      EtpB is a pore-forming outer membrane protein showing TpsB protein features involved in the two-partner secretion system.

      Meli AC, Kondratova M, Molle V, Coquet L, Kajava AV, Saint N.

      J Membr Biol. 230(3):143-54. Pubmed

    • 2009

      Vaccine potentials of an intrinsically unstructured fragment derived from the blood stage-associated Plasmodium falciparum protein PFF0165c.

      Olugbile S, Kulangara C, Bang G, Bertholet S, Suzarte E, Villard V, Frank G, Audran R, Razaname A, Nebie I,[...]

      Infect Immun. 77(12):5701-9. Pubmed

    • 2008

      Three-dimensional structure of canine adenovirus serotype 2 capsid.

      Schoehn G, El Bakkouri M, Fabry CM, Billet O, Estrozi LF, Le L, Curiel DT, Kajava AV, Ruigrok RW, Kremer[...]

      J Virol. 82(7):3192-203. Pubmed

    • 2008

      Origin and evolution of GALA-LRR, a new member of the CC-LRR subfamily: from plants to bacteria?

      Kajava AV, Anisimova M, Peeters N.

      PLoS One. 3(2):e1694. Pubmed

    • 2008

      Longitudinal analyses of immune responses to Plasmodium falciparum derived peptides corresponding to novel blood stage antigens in coastal Kenya.

      Agak GW, Bejon P, Fegan G, Gicheru N, Villard V, Kajava AV, Marsh K, Corradin G.

      Vaccine. 26(16):1963-71. Pubmed