Our Research

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.

Amyloides 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.

To access our bioinformatics tools go to : http://bioinfo.montp.cnrs.fr/

Funding

National Institute of Health (Andrei KAjava)

Commission Européenne (Andrei KAjava & Bernardo Pau)

Publications

2024

AmyloComp: A Bioinformatic Tool for Prediction of Amyloid Co-aggregation. Bondarev SA, Uspenskaya MV, Leclercq J, Falgarone T, Zhouravleva GA, Kajava AV. J Mol Biol. 2024 Jan 5:168437. Pubmed

2023

A STRP-ed definition of Structured Tandem Repeats in Proteins. Monzon AM, Arrías PN, Elofsson A, Mier P, Andrade-Navarro MA, Bevilacqua M, Clementel D, Bateman A, Hirsh L, Fornasari MS, Parisi G, Piovesan D, Kajava AV, Tosatto SCE. J Struct Biol. 2023 Aug 29;215(4):108023. Pubmed
The repetitive structure of DNA clamps: An overlooked protein tandem repeat. Arrías PN, Monzon AM, Clementel D, Mozaffari S, Piovesan D, Kajava AV, Tosatto SCE. J Struct Biol. 2023 Sep;215(3):108001.. Pubmed
Why does the first protein repeat often become the only one? Manasra S, Kajava AV. J Struct Biol. 2023 Sep;215(3):108014. Pubmed
Census of exposed aggregation-prone regions in proteomes. Falgarone T, Villain E, Richard F, Osmanli Z, Kajava AV. Brief Bioinform. 2023 Jul 20;24(4):bbad183. Pubmed
ATR-FTIR spectrum analysis of plasma samples for rapid identification of recovered COVID-19 individuals. Karas BY, Sitnikova VE, Nosenko TN, Dedkov VG, Arsentieva NA, Gavrilenko NV, Moiseev IS, Totolian AA, Kajava AV, Uspenskaya MV. J Biophotonics. 2023 Jul;16(7):e202200166. Pubmed
Pathogenic TRIO variants associated with neurodevelopmental disorders perturb the molecular regulation of TRIO and axon pathfinding in vivo.Bonnet M, Roche F, Fagotto-Kaufmann C, Gazdagh G, Truong I, Comunale F, Barbosa S, Bonhomme M, Nafati N, Hunt D, Rodriguez MP, Chaudhry A, Shears D, Madruga M, Vansenne F, Curie A, Kajava AV, Baralle D, Fassier C, Debant A, Schmidt S. Mol Psychiatry. 2023 Apr;28(4):1527-1544. Pubmed

2022

2021

Identification of a Region in the Common Amino-terminal Domain of Hendra Virus P, V, and W Proteins Responsible for Phase Transition and Amyloid Formation. Salladini E, Gondelaud F, Nilsson JF, Pesce G, Bignon C, Murrali MG, Fabre R, Pierattelli R, Kajava AV, Horvat B, Gerlier D, Mathieu C, Longhi S. Biomolecules 1, 1324 Pubmed
Critical assessment of protein intrinsic disorder prediction. Necci M, Piovesan D; CAID Predictors; DisProt Curators, Tosatto SCE. Nat Methods. 18(5):472-481. Pubmed
RepeatsDB in 2021: improved data and extended classification for protein tandem repeat structures. Paladin L, Bevilacqua M, Errigo S, Piovesan D, Mičetić I, Necci M, Monzon AM, Fabre ML, Lopez JL, Nilsson JF, Rios J, Menna PL, Cabrera M, Buitron MG, Kulik MG, Fernandez-Alberti S, Fornasari MS, Parisi G, Lagares A, Hirsh L, Andrade-Navarro MA, Kajava AV, Tosatto SCE. Nucleic Acids Res. 49(D1):D452-D457 Pubmed

2020

2019

DisProt: intrinsic protein disorder annotation in 2020. Hatos A, Hajdu-Soltész B, Monzon AM, Palopoli N, Álvarez L, Aykac-Fas B, Bassot C, Benítez GI, Bevilacqua M, Chasapi A,[…] Nucleic Acids Res. pii: gkz975. Pubmed
Design of a New [PSI +]-No-More Mutation in SUP35 With Strong Inhibitory Effect on the [PSI +] Prion Propagation. Danilov LG, Matveenko AG, Ryzhkova VE, Belousov MV, Poleshchuk OI, Likholetova DV, Sokolov PA, Kasyanenko NA, Kajava AV, Zhouravleva GA, Bondarev SA. Front Mol Neurosci. 12:274. Pubmed
Tandem repeats lead to sequence assembly errors and impose multi-level challenges for genome and protein databases. Tørresen OK, Star B, Mier P, Andrade-Navarro MA, Bateman A, Jarnot P, Gruca A, Grynberg M, Kajava AV, Promponas VJ, Anisimova M, Jakobsen KS, Linke D. Nucleic Acids Res. 47(21):10994-11006 Pubmed
Prion soft amyloid core driven self-assembly of globular proteins into bioactive nanofibrils. Wang W, Navarro S, Azizyan RA, Baño-Polo M, Esperante SA, Kajava AV, Ventura S. Nanoscale. 11(26):12680-12694. Pubmed
Porins and Amyloids are Coded by Similar Sequence Motifs. Villain E, Nikekhin AA, Kajava AV. 19(6):e1800075 Pubmed
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 DE, Pages M, Bastien P, Kajava AV, Bron P, Hernandez JF, Coux O. Int J Mol Sci. 20(5). 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, Lu JT, Chevalier P, Skládal P, Dvořak P, Rotrekl V, Marks AR, Scheinman MM, Lacampagne A, Meli AC. J Clin Med. 8;7(11) Pubmed
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
BetaSerpentine: a bioinformatics tool for reconstruction of amyloid structures. Bondarev SA, Bondareva OV, Zhouravleva GA, Kajava AV. Bioinformatics. 34(4):599-608 Pubmed
Editorial for special issue « Proteins with tandem repeats: sequences, structures and functions ». Kajava AV, Tosatto SCE. J Struct Biol. 201(2):86-87. Pubmed
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
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
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
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
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, Peeters N. Mol Plant Pathol. 17(4):553-64. Pubmed
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
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
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
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
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
Evolution of proteasome regulators in eukaryotes. Fort P, Kajava AV, Delsuc F, Coux O. Genome Biol Evol. 7:1363-79. Pubmed
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
Structure-based view on [PSI(+)] prion properties. Bondarev SA, Zhouravleva GA, Belousov MV, Kajava AV. Prion. 9:190-9. Pubmed
Designs on a curve. Bazan JF, Kajava AV. Nat Struct Mol Biol. 22:103-5. Pubmed
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
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
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
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 AV, Tosatto SC. Nucleic Acids Res. 42:D352-7. Pubmed
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, Herrera S. PLoS One. 9:e100440. Pubmed
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 P, Kiss I, Bertrand E, Mechler BM, Pradet-Balade B. J Biol Chem. 289:6236-47. Pubmed
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, Smith T, Kajava AV, Spertini F, Corradin G. Malar J. 13:510. Pubmed
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
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
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
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
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
PRDB: Protein Repeat DataBase. Jorda J, Baudrand T, Kajava AV. Proteomics. 12(9):1333-6. Pubmed
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
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, Felger I. 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
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, Konate K, Kajava AV, Schuck P, Druilhe P, Spertini F, Corradin G. 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
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
Malaria vaccine: why is it taking so long? Corradin G, Kajava AV. Expert Rev Vaccines. 9(2):111-4. Pubmed
Protein tandem repeats – the more perfect, the less structured. Jorda J, Xue B, Uversky VN, Kajava AV. FEBS J. 277(12):2673-82. Pubmed
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
Protein homorepeats sequences, structures, evolution, and functions. Jorda J, Kajava AV. Adv Protein Chem Struct Biol. 79:59-88. Pubmed
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
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
T-REKS: identification of Tandem REpeats in sequences with a K-meanS based algorithm. Jorda J, Kajava AV. Bioinformatics. 25(20):2632-8. Pubmed
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
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, Awobusuyi O, Spertini F, Kajava AV, Felger I, Druilhe P, Corradin G. 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 EJ. J Virol. 82(7):3192-203. Pubmed
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
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

Structural bioinformatics and molecular modelling

Andrey KAJAVA

Group Leader (Research Director DR1)

Team Members

Gudrun ALDRIAN (IR-Recherche) +33 (0)4 34 35 95 39
Marie-Therese CHATEAU (Maître de conférences) +33 (0)4 34 35 95 39
Maria Leticia FERRELLI (Chercheur) +33 (0)4 34 35 95 54
Valentin GONAY (Doctorant) +33 (0)4 34 35 95 39
Andrey KAJAVA Chef d'équipe (Chercheur DR1) +33 (0)4 34 35 95 38
Wissal MEFTAH (Stagiaire) +33 (0)4 34 35 95 39
Stefany NECIOSUP (Doctorant) +33 (0)4 34 35 95 39
Zarifa OSMANLI (Doctorant) +33 (0)4 34 35 9