Biochemistry, Biophysics & Structural Biology Department

Biochemistry, Biophysics and Structural Biology Department

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Head: 

Julie Ménétrey

Deputy  heads:

    Benoit D’Autréaux 

Virginie Gervais 

The department is interested in protein architectures and studies how their different structural levels and interactions regulate their functions.

Focus

The B3S teams study soluble and membrane protein assemblies involved in major biological processes of eukaryotic and bacterial cells. 

Our aim is to  understand the molecular mechanisms of biological structures and biochemical reactions at different scales, from electrons and protons via atoms and molecules to multicellular organisms. Successfully introduced new technologies to promote product innovation and upgrades.

Approaches

Biochemical reactions, interactions and enzymatic processes, including large conformational changes and rearrangements within proteins and their complexes, are often initiated by a transfer of subatomic particles – electrons and protons. Studying the atomic structures of proteins with and without ligands can for example help determine how the structure of the active site enables an enzyme to perform its activity.

At molecular scales, biochemical and biophysical analyses as well as structure determination of protein-protein, or protein-nucleic acid complexes, helps in describing the interaction of biological assemblies and understanding biochemical reactions.  In vitro reconstitution of cellular functions leads to an understanding of the regulation of complex processes in vivo.

Research groups

Publications

3888256 B3S 1 chicago-author-date 5 date desc year 36406 https://www.i2bc.paris-saclay.fr/wp-content/plugins/zotpress/
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Combet, Sophie, Raphael Dos Santos Morais, Audrey Comte, et al. 2026. “Weak Protein-Bicelle Binding Quantification via Surface-Based DNA Nanolevers.” European Biophysics Journal: EBJ, ahead of print, March 2. https://doi.org/10.1007/s00249-026-01829-4.
Gobbi Sebinelli, Heitor, Camille Syska, Hafez Razmazma, et al. 2026. “Ist2 Is a Phospholipid Scramblase That Links Lipid Transport at the ER to Organelle Homeostasis.” The Journal of Cell Biology 225 (2): e202502112. https://doi.org/10.1083/jcb.202502112.
Denk, Timo, Paul Monassa, Joanna Musial, et al. 2026. “Structural Basis of Co-Translational N-Myristoylation in Humans.” Nature Communications, ahead of print, January 23. https://doi.org/10.1038/s41467-025-67962-4.
Makulyte, Gabriela, Hasan Safwan-Zaiter, Delphine Goehrig, et al. 2026. “The Proinflammatory Secretome of Senescent Cells Can Be Controlled by a HIF2A-Dependent Upregulation and a FURIN-Dependent Cleavage of the ANGPTL4 Secreted Factor.” Aging Cell 25 (1): e70307. https://doi.org/10.1111/acel.70307.
Hall, Chloe, Philippe Frit, Antonia Kefala-Stavridi, et al. 2025. “Cryo-EM Structures of NHEJ Assemblies with Nucleosomes.” Nature Communications, ahead of print, December 24. https://doi.org/10.1038/s41467-025-67376-2.

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