Examination of the dynamic assembly equilibrium for E. coli ClpB

Proteins. 2015 Nov;83(11):2008-24. doi: 10.1002/prot.24914. Epub 2015 Sep 10.

Abstract

Escherichia coli ClpB is a heat shock protein that belongs to the AAA+ protein superfamily. Studies have shown that ClpB and its homologue in yeast, Hsp104, can disrupt protein aggregates in vivo. It is thought that ClpB requires binding of nucleoside triphosphate to assemble into hexameric rings with protein binding activity. In addition, it is widely assumed that ClpB is uniformly hexameric in the presence of nucleotides. Here we report, in the absence of nucleotide, that increasing ClpB concentration leads to ClpB hexamer formation, decreasing NaCl concentration stabilizes ClpB hexamers, and the ClpB assembly reaction is best described by a monomer, dimer, tetramer, hexamer equilibrium under the three salt concentrations examined. Further, we found that ClpB oligomers exhibit relatively fast dissociation on the time scale of sedimentation. We anticipate our studies on ClpB assembly to be a starting point to understand how ClpB assembly is linked to the binding and disaggregation of denatured proteins.

Keywords: AAA+ motor proteins; SedAnal; Sedfit; analytical ultracentrifugation; chaperones; hexamer; kinetics; protein quality control; protein unfoldases; thermodynamics.

Publication types

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

MeSH terms

  • Endopeptidase Clp
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / metabolism*
  • Heat-Shock Proteins / chemistry*
  • Heat-Shock Proteins / metabolism*
  • Protein Multimerization
  • Protein Unfolding
  • Sodium Chloride
  • Thermodynamics

Substances

  • Escherichia coli Proteins
  • Heat-Shock Proteins
  • Sodium Chloride
  • Endopeptidase Clp
  • ClpB protein, E coli