Molecular determinants of MecA as a degradation tag for the ClpCP protease

J Biol Chem. 2009 Dec 4;284(49):34366-75. doi: 10.1074/jbc.M109.053017. Epub 2009 Sep 18.

Abstract

Regulated proteolysis by ATP-dependent proteases is universal in all living cells. In Bacillus subtilis, the degradation of the competence transcription factor ComK is mediated by a ternary complex involving the adaptor protein MecA and the ATP-dependent protease ClpCP. Here we demonstrate that a C-terminal, 98-amino acid domain of MecA (residues 121-218) serves as a non-recycling, degradation tag and targets a variety of fusion proteins to the ClpCP protease for degradation. MecA-(121-218) facilitates productive oligomerization of ClpC, stimulates the ATPase activity of ClpC, and allows the activated ClpC complex to stably associate with ClpP. Importantly, the ClpCP protease undergoes dynamic cycles of assembly and disassembly, which are triggered by association with MecA and the degradation of MecA, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / chemistry
  • Amino Acids / chemistry
  • Bacillus subtilis / metabolism*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Cloning, Molecular
  • Endopeptidase Clp / chemistry
  • Endopeptidase Clp / metabolism
  • Endopeptidase Clp / physiology*
  • Endopeptidases / chemistry
  • Gene Expression Regulation, Bacterial
  • Heat-Shock Proteins / chemistry
  • Heat-Shock Proteins / metabolism*
  • Models, Biological
  • Peptide Hydrolases / metabolism*
  • Polymerase Chain Reaction
  • Protein Folding
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry

Substances

  • Amino Acids
  • Bacterial Proteins
  • ClpC protein, Bacteria
  • Heat-Shock Proteins
  • Recombinant Fusion Proteins
  • mecA protein, Bacillus subtilis
  • Endopeptidases
  • Peptide Hydrolases
  • Endopeptidase Clp
  • Adenosine Triphosphatases