Crystal Structure of the MecA Degradation Tag |
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Authors: | Feng Wang Ziqing Mei Yutao Qi Chuangye Yan Siheng Xiang Zhiyuan Zhou Qi Hu Jiawei Wang and Yigong Shi |
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Institution: | From the ‡Ministry of Education Protein Science Laboratory and ;§State Key Laboratory of Biomembrane, Center for Structural Biology, School of Life Sciences, and ;¶School of Medicine, Tsinghua University, Beijing 100084, China |
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Abstract: | 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 ? 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 ? 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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