Roger Adams Laboratory, Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, United States.
Roger Adams Laboratory, Department of Biochemistry, University of llinois at Urbana-Champaign, Urbana, United States.
Elife. 2019 Jan 14;8:e42305. doi: 10.7554/eLife.42305.
The secretion of peptides and proteins is essential for survival and ecological adaptation of bacteria. Dual-functional ATP-binding cassette transporters export antimicrobial or quorum signaling peptides in Gram-positive bacteria. Their substrates contain a leader sequence that is excised by an N-terminal peptidase C39 domain at a double Gly motif. We characterized the protease domain (LahT150) of a transporter from a lanthipeptide biosynthetic operon in Lachnospiraceae and demonstrate that this protease can remove the leader peptide from a diverse set of peptides. The 2.0 Å resolution crystal structure of the protease domain in complex with a covalently bound leader peptide demonstrates the basis for substrate recognition across the entire class of such transporters. The structural data also provide a model for understanding the role of leader peptide recognition in the translocation cycle, and the function of degenerate, non-functional C39-like domains (CLD) in substrate recruitment in toxin exporters in Gram-negative bacteria.
肽和蛋白质的分泌对于细菌的生存和生态适应至关重要。双功能的 ATP 结合盒转运蛋白将抗微生物或群体感应肽从革兰氏阳性菌中输出。它们的底物含有一个前导序列，该序列在双甘氨酸基序处被 N 端肽酶 C39 结构域切除。我们对来自厚壁菌门中一个类杆菌生物合成操纵子的转运蛋白的蛋白酶结构域（LahT150）进行了表征，并证明该蛋白酶可以从多种肽中去除前导肽。蛋白酶结构域与共价结合的前导肽的 2.0Å 分辨率晶体结构表明了整个此类转运蛋白家族的底物识别基础。结构数据还为理解前导肽识别在易位循环中的作用以及革兰氏阴性菌中毒素外排体中退化的、无功能的 C39 样结构域 (CLD) 在底物募集中的作用提供了模型。
