Structure of the AAA ATPase p97

Mol Cell. 2000 Dec;6(6):1473-84. doi: 10.1016/s1097-2765(00)00143-x.

Abstract

p97, an abundant hexameric ATPase of the AAA family, is involved in homotypic membrane fusion. It is thought to disassemble SNARE complexes formed during the process of membrane fusion. Here, we report two structures: a crystal structure of the N-terminal and D1 ATPase domains of murine p97 at 2.9 A resolution, and a cryoelectron microscopy structure of full-length rat p97 at 18 A resolution. Together, these structures show that the D1 and D2 hexamers pack in a tail-to-tail arrangement, and that the N domain is flexible. A comparison with NSF D2 (ATP complex) reveals possible conformational changes induced by ATP hydrolysis. Given the D1 and D2 packing arrangement, we propose a ratchet mechanism for p97 during its ATP hydrolysis cycle.

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Adenosine Triphosphatases / chemistry*
  • Adenosine Triphosphatases / metabolism
  • Adenosine Triphosphatases / ultrastructure*
  • Adenosine Triphosphate / metabolism
  • Adenylyl Imidodiphosphate / metabolism
  • Amino Acid Sequence
  • Animals
  • Archaeal Proteins
  • Binding Sites
  • Carrier Proteins / chemistry
  • Cryoelectron Microscopy*
  • Crystallography, X-Ray
  • Fungal Proteins / chemistry
  • Membrane Fusion
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • N-Ethylmaleimide-Sensitive Proteins
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / ultrastructure*
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Peptide Fragments / ultrastructure
  • Pliability
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Rats
  • Saccharomyces cerevisiae Proteins*
  • Sequence Alignment
  • Valosin Containing Protein
  • Vesicular Transport Proteins*

Substances

  • Archaeal Proteins
  • Carrier Proteins
  • Fungal Proteins
  • Nuclear Proteins
  • Peptide Fragments
  • Saccharomyces cerevisiae Proteins
  • Vesicular Transport Proteins
  • Adenylyl Imidodiphosphate
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Adenosine Triphosphatases
  • SEC18 protein, S cerevisiae
  • p97 ATPase
  • N-Ethylmaleimide-Sensitive Proteins
  • Nsf protein, mouse
  • Nsf protein, rat
  • Valosin Containing Protein
  • vat protein, Thermoplasma acidophilum

Associated data

  • PDB/1E32