Conformational stability of the full-atom hexameric model of the ClpB chaperone from Escherichia coli

Biopolymers. 2010 Jan;93(1):47-60. doi: 10.1002/bip.21294.

Abstract

The Escherichia coli heat shock protein ClpB, a member of the Hsp100 family, plays a crucial role in cellular thermotolerance. In co-operation with the Hsp70 chaperone system, it is able to solubilize proteins aggregated by heat shock conditions and refold them into the native state in an ATP-dependent way. It was established that the mechanism of ClpB action depends on the formation of a ring-shaped hexameric structure and the translocation of a protein substrate through an axial channel. The structural aspects of this process are not fully known. By means of homology modeling and protein-protein docking, we obtained a model of the hexameric arrangement of the full-length ClpB protein complexed with ATP. A molecular dynamics simulation of this model was performed to assess its flexibility and conformational stability. The high mobility of the "linker" M-domain, essential for the renaturing activity of ClpB, was demonstrated, and the size and shape of central channel were analyzed. In this model, we propose the coordinates for a loop between b4 and B6 structural elements, not defined in previous structural research, which faces the inside of the channel and may therefore play a role in substrate translocation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / chemistry
  • Adenosine Triphosphatases / metabolism
  • Crystallography, X-Ray
  • Endopeptidase Clp
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / metabolism
  • HSP70 Heat-Shock Proteins / chemistry
  • HSP70 Heat-Shock Proteins / metabolism
  • Heat-Shock Proteins / chemistry*
  • Heat-Shock Proteins / metabolism
  • Models, Molecular*
  • Protein Binding
  • Protein Conformation

Substances

  • Escherichia coli Proteins
  • HSP70 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Endopeptidase Clp
  • Adenosine Triphosphatases
  • ClpB protein, E coli