Structure of cellular ESCRT-III spirals and their relationship to HIV budding

Anil G. Cashikar, Soomin Shim, Robyn Roth, Michael R. Maldazys, John E. Heuser, Phyllis I. Hanson

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

The ESCRT machinery along with the AAA+ ATPase Vps4 drive membrane scission for trafficking into multivesicular bodies in the endocytic pathway and for the topologically related processes of viral budding and cytokinesis, but how they accomplish this remains unclear. Using deep-etch electron microscopy, we find that endogenous ESCRT-III filaments stabilized by depleting cells of Vps4 create uniform membrane-deforming conical spirals which are assemblies of specific ESCRT-III heteropolymers. To explore functional roles for ESCRT-III filaments, we examine HIV-1 Gag-mediated budding of virus-like particles and find that depleting Vps4 traps ESCRT-III filaments around nascent Gag assemblies. Interpolating between the observed structures suggests a new role for Vps4 in separating ESCRT-III from Gag or other cargo to allow centripetal growth of a neck constricting ESCRT-III spiral.

Original languageEnglish
Article numbere02184
JournaleLife
Volume3
DOIs
StatePublished - 2014

Keywords

  • ESCRT
  • HIV-1 budding
  • cell biology
  • deep-etch EM
  • endosome
  • human
  • multivesicular body
  • viruses

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