National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 10010, China.
J Biol Chem. 2012 Aug 3;287(32):26911-20. doi: 10.1074/jbc.M112.368043. Epub 2012 Jun 14.
Recently, it was identified that Pseudomonas aeruginosa competes with rival cells to gain a growth advantage using a novel mechanism that includes two interrelated processes as follows: employing type VI secretion system (T6SS) virulence effectors to lyse other bacteria, and at the same time producing specialized immunity proteins to inactivate their cognate effectors for self-protection against mutual toxicity. To explore the structural basis of these processes in the context of functional performance, the crystal structures of the T6SS virulence effector Tse1 and its complex with the corresponding immunity protein Tsi1 were determined, which, in association with mutagenesis and Biacore analyses, provided a molecular platform to resolve the relevant structural questions. The results indicated that Tse1 features a papain-like structure and conserved catalytic site with distinct substrate-binding sites to hydrolyze its murein peptide substrate. The immunity protein Tsi1 interacts with Tse1 via a unique interactive recognition mode to shield Tse1 from its physiological substrate. These findings reveal both the structural mechanisms for bacteriolysis and the self-protection against the T6SS effector Tse1. These mechanisms are significant not only by contributing to a novel understanding of niche competition among bacteria but also in providing a structural basis for antibacterial agent design and the development of new strategies to fight P. aeruginosa.
最近，研究人员发现铜绿假单胞菌利用一种新的机制与竞争细胞竞争生长优势，该机制包括以下两个相互关联的过程：利用型 VI 分泌系统 (T6SS) 毒力效应器裂解其他细菌，同时产生专门的免疫蛋白来使其同源效应物失活，从而自我保护免受相互毒性的影响。为了在功能表现的背景下探索这些过程的结构基础，确定了 T6SS 毒力效应物 Tse1 及其与相应免疫蛋白 Tsi1 的复合物的晶体结构，结合诱变和 Biacore 分析，为解决相关结构问题提供了分子平台。结果表明，Tse1 具有木瓜蛋白酶样结构和保守的催化位点，具有独特的底物结合位点，可水解其肽聚糖底物。免疫蛋白 Tsi1 通过独特的相互作用识别模式与 Tse1 相互作用，使 Tse1 免受其生理底物的影响。这些发现揭示了细菌裂解和 T6SS 效应物 Tse1 自我保护的结构机制。这些机制不仅有助于对细菌生态位竞争的新理解，而且为抗菌剂设计和对抗铜绿假单胞菌的新策略提供了结构基础。
