Journal of Biological Chemistry
Volume 284, Issue 49, 4 December 2009, Pages 34376-34381
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Protein Synthesis, Post-Translational Modification, and Degradation
Crystal Structure of the MecA Degradation Tag*

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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 Å resolution, which reveals a previously uncharacterized α/β 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 Å 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.

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The atomic coordinates and structure factors (codes 3JTP, 3JTO, and 3JTN) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

*

This work was supported by grants from the Ministry of Science and Technology (Grant 2009CB918801), Tsinghua University 985 Phase II funds, Project 30888001 supported by the National Natural Science Foundation of China, and Beijing Municipal Commissions of Education and Science and Technology.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. 1.

1

These authors contributed equally to this work.