Molecular perspectives on p97-VCP: progress in understanding its structure and diverse biological functions

J Struct Biol. 2004 Apr-May;146(1-2):44-57. doi: 10.1016/j.jsb.2003.11.014.

Abstract

The 97-kDa valosin-containing protein (p97 or VCP) is a type-II AAA ( ATPases associated with a variety of activities) ATPases, which are characterized by possessing two conserved ATPase domains. VCP forms a stable homo-hexameric structure, and this two-tier ring-shaped complex acts as a molecular chaperone that mediates many seemingly unrelated cellular activities. The involvement of VCP in the ubiquitin-proteasome degradation pathway and the identification of VCP cofactors provided us important clues to the understanding of how this molecular chaperone works. In this review, we summarize the reported biological functions of VCP and explore the molecular mechanisms underlying the diverse cellular functions. We discuss the structural and biochemical studies, and elucidate how this sophisticated enzymatic machine converts chemical energy into the mechanical forces required for the chaperone activity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adenosine Triphosphatases
  • Cell Cycle Proteins / chemistry*
  • Cell Cycle Proteins / physiology*
  • Molecular Chaperones / chemistry
  • Molecular Chaperones / physiology
  • Molecular Motor Proteins
  • Protein Structure, Quaternary
  • Valosin Containing Protein

Substances

  • Cell Cycle Proteins
  • Molecular Chaperones
  • Molecular Motor Proteins
  • Adenosine Triphosphatases
  • Valosin Containing Protein