Substrate recognition by the AAA+ chaperone ClpB

Nat Struct Mol Biol. 2004 Jul;11(7):607-15. doi: 10.1038/nsmb787. Epub 2004 Jun 20.

Abstract

The AAA+ protein ClpB cooperates with the DnaK chaperone system to solubilize and refold proteins from an aggregated state. The substrate-binding site of ClpB and the mechanism of ClpB-dependent protein disaggregation are largely unknown. Here we identified a substrate-binding site of ClpB that is located at the central pore of the first AAA domain. The conserved Tyr251 residue that lines the central pore contributes to substrate binding and its crucial role was confirmed by mutational analysis and direct crosslinking to substrates. Because the positioning of an aromatic residue at the central pore is conserved in many AAA+ proteins, a central substrate-binding site involving this residue may be a common feature of this protein family. The location of the identified binding site also suggests a possible translocation mechanism as an integral part of the ClpB-dependent disaggregation reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Amino Acid Sequence
  • Binding, Competitive
  • Models, Chemical
  • Molecular Chaperones / metabolism*
  • Molecular Sequence Data
  • Mutagenesis
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Tyrosine / metabolism

Substances

  • Molecular Chaperones
  • Tyrosine
  • Adenosine Triphosphatases