Structure and Fonction of ESCRT-III complex
The endosomal sorting complex required for transport (ESCRT) machinery catalyzes many divergent membrane remodeling processes including the formation of multivesicular endosomes, cytokinesis, nuclear envelope reformation, membrane repair, exosome biogenesis, enveloped virus budding and many other processes.
Common to all ESCRT-catalyzed processes in eukaryotes, archaea and bacteria is the recruitment of ESCRT-III proteins that polymerize to generate and/or to stabilize membranes with either flat, negatively or positively curved geometries. The principal function of the polymers is to induce membrane constriction via outside-in fission of tubular structures with ESCRT-III protein coats on the outside of a membrane tube or inside-out fission with ESCRT-III polymers assembled within membrane neck/tube structures formed during vesicle and virus budding or at the cytokinetic midbody.
Humans express eight ESCRT-III proteins (named CHMP) that can comprise several isoforms per member. ESCRT-III composed of CHMP4, CHMP2 and CHMP3 constitute a minimal machinery that together with VPS4 catalyzes membrane fission from within membrane necks and catalizes the HIV budding.
Our project aims at understanding the structural organization of the ESCRT-III polymer composed of the CHMP2A and CHMP3 proteins in order to obtain information on the filament polymerization process and the mode of interaction with the membrane. In collaboration with the electron microscopy platform of the IBS, we intend to visualize ESCRT-III polymers at the site of budding of viruses such as HIV, which will allow to better understand the role of ESCRT-III polymers in membrane neck constriction and membrane fission.
Selected publications :
- Structural basis of CHMP2A–CHMP3 ESCRT-III polymer assembly and membrane cleavage
Kimi Azad, Delphine Guilligay, Cecile Boscheron, Sourav Maity, Nicola de Franceschi, Guidenn Sulbaran, Gregory Effantin, Haiyan Wang, Jean-Philippe Kleman, Patricia Bassereau, Guy Schoehn, Wouter Roos, Ambroise Desfosses, Winfried Weissenhorn
Nature Structural and Molecular Biology, 2022, 30 (1), pp.81-90.
- The ESCRT-III isoforms CHMP2A and CHMP2B display different effects on membranes upon polymerization
Maryam Alqabandi, Nicola de Franceschi, Sourav Maity, Nolwenn Miguet, Marta Bally, Wouter H Roos, Winfried Weissenhorn, Patricia Bassereau, Stéphanie Mangenot
BMC Biology, 2021, 19 (1), pp.66.
- Human ESCRT-III polymers assemble on positively curved membranes and induce helical membrane tube formation
Aurélie Bertin, Nicola de Franceschi, Eugenio de La Mora, Sourav Maiti, Maryam Alqabandi, Nolwenn Miguet, Aurelie Di Cicco, Wouter H Roos, Stéphanie Mangenot, Winfried Weissenhorn, Patricia Bassereau
Nature Communications, 2020