The linker region plays a regulatory role in assembly and activity of the Vps4 AAA ATPase

J Biol Chem. 2013 Sep 13;288(37):26810-9. doi: 10.1074/jbc.M113.497032. Epub 2013 Aug 2.


The AAA-type ATPase Vps4 functions with components of the ESCRT (endosomal sorting complex required for transport) machinery in membrane fission events that are essential for endosomal maturation, cytokinesis, and the formation of retroviruses. A key step in these events is the assembly of monomeric Vps4 into the active ATPase complex, which is aided in part by binding of Vps4 via its N-terminal MIT (microtubule interacting and trafficking) domain to its substrate ESCRT-III. We found that the 40-amino acid linker region between the MIT and the ATPase domain of Vps4 is not required for proper function but plays a role in regulating Vps4 assembly and ATPase activity. Deletion of the linker is expected to bring the MIT domains into close proximity to the central pore of the Vps4 complex. We propose that this localization of the MIT domain in linker-deleted Vps4 mimics a repositioning of the MIT domain normally caused by binding of Vps4 to ESCRT-III. This structure would allow the Vps4 complex to engage ESCRT-III subunits with both the pore and the MIT domain simultaneously, which might be essential for the ATP-driven disassembly of ESCRT-III.

Keywords: ATPases; Endosomes; Enzyme Mechanisms; Membrane; Yeast.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Amino Acid Sequence
  • Cytokinesis
  • DNA Mutational Analysis
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • Endosomes / metabolism
  • Gene Expression Regulation, Fungal*
  • Microtubules / metabolism
  • Molecular Sequence Data
  • Mutation
  • Plasmids / metabolism
  • Protein Binding
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sequence Homology, Amino Acid


  • Endosomal Sorting Complexes Required for Transport
  • Saccharomyces cerevisiae Proteins
  • VPS4 protein, S cerevisiae
  • Adenosine Triphosphatases