Structural basis for antiactivation in bacterial quorum sensing
Structural basis for antiactivation in bacterial quorum sensing
复制标题
DOI：
10.1073/pnas.0704843104
复制
发表时间：
2007-10-16
影响因子：
11.1
通讯作者：
Chen, Lingling
中科院分区：
文献类型：
--
作者：
Chen, Guozhou;Jeffrey, Philip D.;Chen, Lingling
细菌可以通过它们产生和释放的可扩散的信号分子进行交流，以协调它们的行为对环境的反应。信号分子浓度通常与细菌种群密度成正比，当达到反映细菌群体数量的临界浓度时，包括毒力、共生和水平基因转移在内的特定行为被激活。许多革兰氏阴性细菌的群体感应调节涉及酰化高丝氨酸内酯信号，这些信号通过与LuxR类型的酰化高丝氨酸内酯反应转录因子结合而被感知。根瘤菌群中的细菌利用LuxR型转录激活剂TraR进行群体感应，其活性通过与TRAM抗激活剂的相互作用进一步调节。在本研究中，我们从结晶学的角度确定了根瘤菌TRAR-TRAM抗活复合体的三维结构。菌株NGR234。出乎意料的是，抗激活剂TraM在不同于其DNA结合基序的位置与TraR结合，并诱导蛋白质的变构构象变化，从而阻止DNA结合。结构分析揭示了高度保守的TRAR-TRAM界面，并提出了抗活性复合体的形成机制。这种结构可能为控制量子感应调节的微生物活性提供替代策略，包括改善传染病和抗生素耐药性。此外，抗激活的结构基础呈现了一种调控相互作用，提供了与转录调控和信号转导领域相关的一般见解。
Bacteria can communicate via diffusible signal molecules they generate and release to coordinate their behavior in response to the environment. Signal molecule concentration is often proportional to bacterial population density, and when this reaches a critical concentration, reflecting a bacterial quorum, specific behaviors including virulence, symbiosis, and horizontal gene transfer are activated. Quorum-sensing regulation in many Gramnegative bacteria involves acylated homoserine lactone signals that are perceived through binding to LuxR-type, acylated-homoserine-lactone-responsive transcription factors. Bacteria of the rhizobial group employ the LuxR-type transcriptional activatorTraR in quorum sensing, and its activity is further regulated through interactions with the TraM antiactivator. In this study, we have crystallographically determined the 3D structure of the TraR-TraM antiactivation complex from Rhizobium sp. strain NGR234. Unexpectedly, the antiactivatorTraM binds to TraR at a site distinct from its DNA-binding motif and induces an allosteric conformational change in the protein, thereby preventing DNA binding. Structural analysis reveals a highly conserved TraR-TraM interface and suggests a mechanism for antiactivation complex formation. This structure may inform alternative strategies to control quorumsensing-regulated microbial activity including amelioration of infectious disease and antibiotic resistance. In addition, the structural basis of antiactivation presents a regulatory interaction that provides general insights relevant to the field of transcription regulation and signal transcluction.