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 H Roos, Ambroise Desfosses, Winfried Weissenhorn
The endosomal sorting complex required for transport (ESCRT) is a highly conserved protein machinery that drives a divers set of physiological and pathological membrane remodeling processes. However, the structural basis of ESCRT-III polymers stabilizing, constricting and cleaving negatively curved membranes is yet unknown. Here we present cryo-EM structures of membrane-coated CHMP2A-CHMP3 filaments from Homo sapiens of two different diameters at 3.3 and 3.6 Å resolution. The structures reveal helical filaments assembled by CHMP2A-CHMP3 heterodimers in the open ESCRT-III conformation, which generates a partially positive charged membrane interaction surface, positions short N-terminal motifs for membrane interaction and the C-terminal VPS4 target sequence toward the tube interior...
January 5, 2023: Nature Structural & Molecular Biology