Nucleoproteins of Negative Strand RNA Viruses; RNA Binding, Oligomerisation and Binding to Polymerase Co-Factor

Commentary on Tawar, R.G.; Duquerroy, S.; Vonrhein, C.; Varela, P.F.; Damier-Piolle, L.; Castagné, N.; MacLellan, K.; Bedouelle, H.; Bricogne, G.; Bhella, D.; Eléouët, J.-F.; Rey, F.A. Crystal structure of a nucleocapsid-like nucleoprotein-RNA complex of respiratory syncytial virus. Science 2009, 326, 1279–1283

Biologie structurale de complexes protéine:ARN

This manuscript presents my research activities, from my Ph.D. in the laboratory of biochemistry at the École polytechnique to my current CNRS position at the Institut de Biologie Structurale. During these years, through use of various modern structural biology techniques, I have sought to understand how interactions of biological partners underpin different processes. My early work focused on the mechanisms of specificity of different aminoacyl-tRNA synthetases and helped to explain the molecular basis of their fidelity during protein translation. After joining the CNRS, I discovered another research field: the world of viruses and their replication machines. In particular, I have contributed to the great adventure of the influenza virus replication complex, an adventure that led to the resolution of the structure of the full polymerase trimer. Far from being the end of the project, I am now trying to understand influenza polymerase assembly and its cellular dynamic, and am extending this work towards other viral replication machines.Ce manuscrit résume mes années passées dans la recherche, depuis ma thèse au laboratoire debiochimie de l’École Polytechnique jusqu’au poste de chargé de recherche CNRS que j’occupe maintenant àl’Institut de Biologie Structurale. Durant ces années, mes travaux ont visé à détailler par différentestechniques de la biologie structurale, des constituants du vivant ayant vocation à interagir entre eux en vuede l’accomplissement d’un processus biologique. Une partie de ces travaux a consisté à étudier lesmécanismes de la spécificité du fonctionnement des aminoacyl-ARNt synthétases, et ainsi apporter desréponses quant aux bases moléculaires de la fidélité du processus traductionnel. Mon recrutement par leCNRS s’est accompagné d’une mobilité thématique, me faisant découvrir un autre monde, celui des virus etde leurs complexes réplicatifs. J’ai notamment pris part à la grande aventure visant à détailler lesconstituants du complexe réplicatif du virus de la grippe, aventure qui a abouti à la résolution de lastructure du complexe polymérasique grippal. Loin de considérer cette dernière comme une finalité,j’ambitionne maintenant de comprendre son assemblage, d’étendre ces travaux à d’autres des complexesréplicatifs mais tout en intégrant la dynamique cellulaire associée

Capsid proteins of enveloped viruses as antiviral drug targets.

International audienceViral proteins have enabled the design of selective and efficacious treatments for viral diseases. While focus in this area has been on viral enzymes, it appears that multifunctional viral proteins may be even more susceptible to small molecule interference. As exemplified by HIV capsid, small molecule inhibitors can bind to multiple binding sites on the capsid protein and induce or prevent protein interactions and conformational changes. Resistance selection is complicated by the fact that the capsid proteins have to engage in different protein interactions at different times of the life cycle. Viral capsid assembly and disassembly have therefore emerged as highly sensitive processes that could deliver a new generation of antiviral agents across viral diseases

Advances in Structural Virology via Cryo-EM in 2022

In recent years, cryo-electron microscopy (cryo-EM) has emerged as an important standalone technique within structural biology [...

Editorial overview: virus structure and function.

International audienc

In Vitro/In Vivo Production of tRNA for X-Ray Studies

International audiencetRNAs occupy a central role in the cellular life, and they are involved in a broad range of biological processes that relies on their interaction with proteins and RNA. Crystallization and structure resolution of tRNA or/and tRNA/partner complexes can yield in valuable information on structural organizations of key elements of cellular machinery. However, crystallization of RNA, is often challenging. Here we review two methods to produce and purify tRNA in quantity and quality to perform X-ray studies

Structure of the Dimerization Domain of the Rabies Virus Phosphoprotein ▿

The crystal structure of the dimerization domain of rabies virus phosphoprotein was determined. The monomer consists of two α-helices that make a helical hairpin held together mainly by hydrophobic interactions. The monomer has a hydrophilic and a hydrophobic face, and in the dimer two monomers pack together through their hydrophobic surfaces. This structure is very different from the dimerization domain of the vesicular stomatitis virus phosphoprotein and also from the tetramerization domain of the Sendai virus phosphoprotein, suggesting that oligomerization is conserved but not structure