Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, 31077, Toulouse, France.
Laboratoire de Microbiologie et de Génétique Moléculaires, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, 31062, Toulouse, France.
Nat Commun. 2019 Feb 15;10(1):782. doi: 10.1038/s41467-019-08747-4.
SecB chaperones assist protein export by binding both unfolded proteins and the SecA motor. Certain SecB homologs can also control toxin-antitoxin (TA) systems known to modulate bacterial growth in response to stress. In such TA-chaperone (TAC) systems, SecB assists the folding and prevents degradation of the antitoxin, thus facilitating toxin inhibition. Chaperone dependency is conferred by a C-terminal extension in the antitoxin known as chaperone addiction (ChAD) sequence, which makes the antitoxin aggregation-prone and prevents toxin inhibition. Using TAC of Mycobacterium tuberculosis, we present the structure of a SecB-like chaperone bound to its ChAD peptide. We find differences in the binding interfaces when compared to SecB-SecA or SecB-preprotein complexes, and show that the antitoxin can reach a functional form while bound to the chaperone. This work reveals how chaperones can use discrete surface binding regions to accommodate different clients or partners and thereby expand their substrate repertoire and functions.
SecB 伴侣蛋白通过结合未折叠的蛋白质和 SecA 马达来协助蛋白质输出。某些 SecB 同源物还可以控制毒素-抗毒素 (TA) 系统，这些系统已知可以响应应激调节细菌生长。在这种 TA-伴侣蛋白 (TAC) 系统中，SecB 协助折叠并防止抗毒素降解，从而促进毒素抑制。伴侣蛋白依赖性由抗毒素中的 C 末端延伸赋予，称为伴侣蛋白成瘾 (ChAD) 序列，该序列使抗毒素易于聚集并阻止毒素抑制。使用结核分枝杆菌的 TAC，我们展示了与它的 ChAD 肽结合的 SecB 样伴侣蛋白的结构。我们发现与 SecB-SecA 或 SecB-前体复合物相比，结合界面存在差异，并表明当与伴侣蛋白结合时，抗毒素可以达到功能形式。这项工作揭示了伴侣蛋白如何使用离散的表面结合区域来容纳不同的客户或合作伙伴，从而扩展它们的底物谱和功能。
