Center for Integrated Protein Science Munich CIPSM, Department of Chemistry, Technische Universität München, Lichtenbergstr. 4, 85747 Garching (Germany).
Angew Chem Int Ed Engl. 2015 Mar 16;54(12):3598-602. doi: 10.1002/anie.201409325. Epub 2015 Jan 28.
Listeria monocytogenes is a devastating bacterial pathogen. Its virulence and intracellular stress tolerance are supported by caseinolytic protease P (ClpP), an enzyme that is conserved among bacteria. L. monocytogenes expresses two ClpP isoforms that are only distantly related by sequence and differ in catalysis, oligomerization, active-site composition, and N-terminal interaction sites for associated AAA(+) chaperones. The crystal structure of the ClpP1/2 heterocomplex from L. monocytogenes was solved, and in combination with biochemical studies, it provides insights into the mode of action. The results demonstrate that structural interlocking of LmClpP1 with LmClpP2 leads to the formation of a tetradecamer, aligns all 14 active sites, and enhances proteolytic activity. Furthermore, the catalytic center was identified as being responsible for the transient stability of ClpPs.
李斯特菌是一种具有破坏性的细菌病原体。其毒力和细胞内应激耐受能力得到了蛋白酶 P（ClpP）的支持，这种酶在细菌中是保守的。李斯特菌表达两种 ClpP 同工型，它们仅在序列上存在远缘关系，在催化、寡聚化、活性位点组成以及与相关的 AAA(+)伴侣蛋白的 N 端相互作用位点方面存在差异。来自李斯特菌的 ClpP1/2 异源复合物的晶体结构已被解决，并且与生化研究相结合，为作用模式提供了深入的了解。结果表明，LmClpP1 与 LmClpP2 的结构互锁导致形成十四聚体，使所有 14 个活性位点对齐，并增强了蛋白水解活性。此外，鉴定出催化中心负责 ClpP 的瞬时稳定性。
