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The AAA ATPase Vps4 binds ESCRT-III substrates through a repeating array of dipeptide-binding pockets

Han Han1, Nicole Monroe1, Wesley I Sundquist1

  • 1Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States.

Elife
|November 23, 2017
PubMed

Insights

The AAA ATPase Vps4 disassembles ESCRT-III filaments for membrane fission. A new high-resolution structure reveals how Vps4 binds ESCRT-III peptides via specific pockets, supporting a conveyor belt model for filament disassembly.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Structural Biology

Background:

  • The AAA ATPase Vps4 is crucial for membrane fission by remodeling ESCRT-III filaments.
  • Previous studies provided a lower-resolution structure of Vps4.

Purpose of the Study:

  • To determine the high-resolution structure of Vps4 bound to an ESCRT-III peptide substrate.
  • To elucidate the molecular mechanism of ESCRT-III filament disassembly by Vps4.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) to obtain a 3.2 Å resolution structure.
  • Structural analysis of Vps4-ESCRT-III peptide interactions.

Main Results:

  • A 3.2 Å structure of Vps4 bound to an ESCRT-III peptide was determined.
  • The ESCRT-III peptide adopts a β-strand conformation, interacting with five Vps4 subunits.
  • Specific binding pockets in Vps4 (pore loop 1) accommodate diverse residues, with main chain hydrogen bonds orienting the substrate.
  • A 'conveyor belt' model for ATP-dependent translocation and disassembly is supported.

Conclusions:

  • The structure provides detailed insights into Vps4-mediated ESCRT-III filament disassembly.
  • The findings support a model where Vps4 uses ATP binding and hydrolysis to translocate and disassemble the filament.
  • This mechanism is key for membrane fission processes.
Keywords:
AAA ATPaseESCRT pathwaybiochemistrybiophysicscryo-EMmembrane fissionnonestructural biologystructure

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