Effect of temperature on the self-assembly of the Escherichia coli ClpA molecular chaperone

Biochemistry. 2010 Nov 16;49(45):9820-9. doi: 10.1021/bi101136d. Epub 2010 Oct 22.

Abstract

Protein quality control pathways rely upon ATP-dependent proteases, such as Escherichia coli ClpAP, to perform maintenance roles in the cytoplasm of the cell. ATP-dependent proteases remove misfolded and partially synthesized proteins. This action is particularly important in situations where an unregulated accumulation of such proteins will have a deleterious effect on the cell. ClpAP is composed of a tetradecameric serine protease, ClpP (21.6 kDa monomer), and the ATPase/protein unfoldase ClpA (84.2 kDa monomer). ClpA also uses its protein unfolding activity to remodel proteins and protein complexes; thus, in the absence of the proteolytic component, ClpA is considered a molecular chaperone. Previous reports, by others, suggested that ClpA exists in a monomer-dimer equilibrium at 4 °C. In contrast, using a combination of sedimentation velocity, sedimentation equilibrium, and dynamic light scattering, we recently reported that ClpA exists in a monomer-tetramer equilibrium at 25 °C. Here we report an investigation of the effect of temperature on the self-association of the E. coli ClpA protein unfoldase using analytical ultracentrifugation techniques. The results of sedimentation velocity and sedimentation equilibrium experiments performed at multiple loading concentrations of ClpA over a range of temperatures from 3.9 to 38.2 °C are discussed. Sedimentation velocity experiments show a decrease in weight average s(20,w) at the extremes of temperature. This result, along with extensive sedimentation equilibrium data and analysis, suggests the presence of a dimeric intermediate of ClpA that is differentially populated as a function of temperature. Further, analysis of sedimentation equilibrium data as a function of temperature led us to propose a monomer-dimer-tetramer equilibrium to describe the temperature dependence of ClpA self-assembly in the absence of nucleotide.

Publication types

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

MeSH terms

  • Dimerization
  • Endopeptidase Clp / biosynthesis
  • Endopeptidase Clp / chemistry*
  • Endopeptidase Clp / isolation & purification
  • Endopeptidase Clp / metabolism
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / biosynthesis
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / isolation & purification
  • Escherichia coli Proteins / metabolism
  • Fractionation, Field Flow / methods
  • Hydrogen-Ion Concentration
  • Molecular Weight
  • Thermodynamics
  • Ultracentrifugation

Substances

  • Escherichia coli Proteins
  • ClpA protease, E coli
  • Endopeptidase Clp