J proteins catalytically activate Hsp70 molecules to trap a wide range of peptide sequences

Mol Cell. 1998 Nov;2(5):593-603. doi: 10.1016/s1097-2765(00)80158-6.

Abstract

Proteins of the Hsp70 family of ATPases, such as BiP, function together with J proteins to bind polypeptides in numerous cellular processes. Using a solid phase binding assay, we demonstrate that a conserved segment of the J proteins, the J domain, catalytically activates BiP molecules to bind peptides in its immediate vicinity. The J domain interacts with the ATP form of BiP and stimulates hydrolysis resulting in the rapid trapping of peptides, which are then only slowly released upon nucleotide exchange. Activation by the J domain allows BiP to trap peptides or proteins that it would not bind on its own. These results explain why BiP and probably all other Hsp70s can interact with a wide range of substrates and suggest that the J partner primarily determines the substrate specificity of Hsp70s.

Publication types

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

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Adenosine Triphosphatases / metabolism
  • Adenosine Triphosphate / metabolism
  • Binding Sites
  • Chromatography, High Pressure Liquid
  • Enzyme Activation
  • Fungal Proteins / chemistry
  • Fungal Proteins / isolation & purification
  • Fungal Proteins / metabolism*
  • HSP70 Heat-Shock Proteins / isolation & purification
  • HSP70 Heat-Shock Proteins / metabolism*
  • Heat-Shock Proteins*
  • Kinetics
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Membrane Transport Proteins*
  • Models, Biological
  • Nucleotides / metabolism
  • Peptides / chemical synthesis
  • Peptides / metabolism*
  • Protein Conformation
  • Saccharomyces cerevisiae Proteins*
  • Substrate Specificity
  • Surface Plasmon Resonance

Substances

  • Fungal Proteins
  • HSP70 Heat-Shock Proteins
  • Heat-Shock Proteins
  • KAR2 protein, yeast
  • Membrane Proteins
  • Membrane Transport Proteins
  • Nucleotides
  • Peptides
  • SEC63 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Adenosine Triphosphatases