Human ESCRT-III polymers assemble on positively curved membranes and induce helical membrane tube formation

Nat Commun. 2020 May 29;11(1):2663. doi: 10.1038/s41467-020-16368-5.

Abstract

Endosomal sorting complexes for transport-III (ESCRT-III) assemble in vivo onto membranes with negative Gaussian curvature. How membrane shape influences ESCRT-III polymerization and how ESCRT-III shapes membranes is yet unclear. Human core ESCRT-III proteins, CHMP4B, CHMP2A, CHMP2B and CHMP3 are used to address this issue in vitro by combining membrane nanotube pulling experiments, cryo-electron tomography and AFM. We show that CHMP4B filaments preferentially bind to flat membranes or to tubes with positive mean curvature. Both CHMP2B and CHMP2A/CHMP3 assemble on positively curved membrane tubes. Combinations of CHMP4B/CHMP2B and CHMP4B/CHMP2A/CHMP3 are recruited to the neck of pulled membrane tubes and reshape vesicles into helical "corkscrew-like" membrane tubes. Sub-tomogram averaging reveals that the ESCRT-III filaments assemble parallel and locally perpendicular to the tube axis, highlighting the mechanical stresses imposed by ESCRT-III. Our results underline the versatile membrane remodeling activity of ESCRT-III that may be a general feature required for cellular membrane remodeling processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / metabolism
  • Biochemical Phenomena
  • Cryoelectron Microscopy
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • Humans
  • Membranes, Artificial*
  • Nanotubes
  • Polymerization
  • Protein Binding / physiology
  • Protein Multimerization
  • Stress, Mechanical*
  • Vacuolar Proton-Translocating ATPases / metabolism

Substances

  • CHMP2A protein, human
  • CHMP2B protein, human
  • CHMP3 protein, human
  • CHMP4B protein, human
  • Endosomal Sorting Complexes Required for Transport
  • Membranes, Artificial
  • Vacuolar Proton-Translocating ATPases
  • ATPases Associated with Diverse Cellular Activities
  • VPS4A protein, human