ESCRT-III membrane neck cleavage mechanism revealed

The endosomal sorting complex required for transport (ESCRT) machinery catalyzes many divergent membrane-remodeling processes such as membrane repair, enveloped virus budding and cytokinesis, amongst others. Dysfunction of the ESCRT machinery is associated with a diverse set of pathologies such as cancer or neuronal deficiencies. Notably members of the ESCRT-III protein family are conserved in all kingdoms of life and have been proposed to polymerize on membranes and remodel them to the point of fission in conjunction with the ATPase VPS4.
In a collaborative effort, researchers from the IBS (EBEV, MEM, MICA, I2SR), the Curie Institute in Paris and the University of Groningen provide first high resolution cryoEM structures of ESCRT-III filaments composed of CHMP2A and CHMP3 forming membrane-coated tubular structures in vitro that resemble ESCRT-III filament architectures at virus or vesicle budding sites or the cytokinetic midbody. The structures provide molecular details of helical filament polymerization, membrane interaction and support a model that predicts processive filament sliding upon remodeling by VPS4. Analysis of single ESCRT-III membrane tubes confirmed that the ESCRT-III polymers are constricted and cleaved by VPS4 in vitro, suggesting that they constitute a minimal machinery that can cleave membrane necks via membrane fission.

Structural basis of CHMP2A-CHMP3 ESCRT-III polymer assembly and membrane cleavage. Azad K, Guilligay D, Boscheron C, Maity S, De Franceschi N, Sulbaran G, Effantin G, Wang H, Kleman JP, Bassereau P, Schoehn G, Roos WH, Desfosses A, Weissenhorn W. Nat Struct Mol Biol. 2023 Jan ;30(1):81-90. DOI : 10.1038/s41594-022-00867-8

Contact : Winfried Weissenhorn (IBS/Entry and Budding of Enveloped Viruses Group)