8 February

Combining coevolution-driven predictions and experiments to elucidate the complexity of protein interaction networks

Le 8 February - 09h-10h

Predicting protein-protein interactions and characterizing their structural organization provides essential information to elucidate the molecular mechanisms underlying cross-talk between cellular pathways. Exploiting coevolution information has emerged over the last years as a major strategy for predicting the mode of recognition between proteins. Our recent methodological developments [1, 2] have provided key insights to unravel the regulatory subtleties that might exist between pairs of interacting proteins [3, 4]. The advent of machine learning in the field, culminating in the Alphafold breakthrough, is pushing the boundaries from analyses of binary to multiple interactions. We will discuss strategies to further integrate predictions with experimental assessment and elucidate the complexity of the molecular logic behind large networks of proteins interacting together.

[1] Quignot C, Granger P, Chacon P, Guerois R, Andreani J. Atomic-level evolutionary information improves protein-protein interface scoring. Bioinformatics. 2021. https://doi.org/10.1093/bioinformatics/btab254.

[2] Quignot C, Postic G, Bret H, Rey J, Granger P, Murail S, Chacón P, Andreani J, Tufféry P, Guerois R. InterEvDock3: a combined template-based and free docking server with increased performance through explicit modeling of complex homologs and integration of covariation-based contact maps. Nucleic Acids Res. 2021 Jul 2;49(W1):W277-W284. https://doi.org/10.1093/nar/gkab358

[3] Acharya A, Kasaciunaite K, Göse M, Kissling V, Guerois R, Seidel R, Cejka P. Distinct RPA domains promote recruitment and the helicase-nuclease activities of Dna2. Nat Commun. 2021 12(1):6521. https://doi.org/10.1038/s41467-021-26863-y.

[4] Pyatnitskaya A, Andreani J, Guerois R, De Muyt A, Borde V. The Zip4 protein directly couples meiotic crossover formation to synaptonemal complex assembly. Genes Dev. 2022 36(1-2):53-69. https://doi.org/10.1101/gad.348973.121.

Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, University Paris Saclay, Gif sur Yvette, France
Institut Curie
Invité(es) par
Institut Curie