Crystal structure of the MecA degradation tag

J Biol Chem. 2009 Dec 4;284(49):34376-81. doi: 10.1074/jbc.M109.053033. Epub 2009 Oct 2.


MecA is an adaptor protein that regulates the assembly and activity of the ATP-dependent ClpCP protease in Bacillus subtilis. MecA contains two domains. Although the amino-terminal domain of MecA recruits substrate proteins such as ComK and ComS, the carboxyl-terminal domain (residues 121-218) has dual roles in the regulation and function of ClpCP protease. MecA-(121-218) facilitates the assembly of ClpCP oligomer, which is required for the protease activity of ClpCP. This domain was identified to be a non-recycling degradation tag that targets heterologous fusion proteins to the ClpCP protease for degradation. To elucidate the mechanism of MecA, we determined the crystal structure of MecA-(121-218) at 2.2 A resolution, which reveals a previously uncharacterized alpha/beta fold. Structure-guided mutagenesis allows identification of surface residues that are essential for the function of MecA. We also solved the structure of a carboxyl-terminal domain of YpbH, a paralogue of MecA in B. subtilis, at 2.4 A resolution. Despite low sequence identity, the two structures share essentially the same fold. The presence of MecA homologues in other bacterial species suggests conservation of a large family of unique degradation tags.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacillus subtilis / metabolism*
  • Bacterial Proteins / chemistry*
  • Chromatography, Gel
  • Crystallography, X-Ray / methods
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Peptide Hydrolases / chemistry
  • Polymerase Chain Reaction
  • Protein Conformation
  • Protein Folding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid


  • Bacterial Proteins
  • mecA protein, Bacillus subtilis
  • Peptide Hydrolases

Associated data

  • PDB/3JTN
  • PDB/3JTO
  • PDB/3JTP