STRUCTURE AND FUNCTION OF OUTER MEMBRANE PROTEINS

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 A. 鼠疫耶尔森菌纤溶酶原激活剂 Pla 的结构。 Pla 是 Omptin 家族的成员，该家族是广泛存在于革兰氏阴性细菌中的外膜蛋白酶家族。虽然大多数 omptins（例如大肠杆菌 OmpT）的生理作用尚不清楚，但鼠疫耶尔森菌 Pla 通过裂解（激活）人纤溶酶原，在黑死病和肺鼠疫的毒力中具有非常重要的作用。 我们正在研究 Pla 的高分辨率晶体结构，以获得有关 omptins 催化机制和底物特异性的结构基础的信息。 B.全长自动转运器的结构。 自转运蛋白分泌机制是致病性革兰氏阴性菌跨外膜 (OM) 分泌毒力因子的最常见机制。此外，自转运蛋白因在细菌细胞表面展示蛋白质而引起了生物技术和生物医学界的兴趣。尽管它们很重要，但自动运输机的乘客域通过 OM 的机制仍不清楚。经典观点认为，Ф-桶结构域提供了展开的乘客移动的管道，其中能量是由 OM 细胞外侧富含Ф-链的乘客的矢量折叠提供的。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A. Structure of the plasminogen activator Pla from Yersinia pestis. Pla is a member of the omptin family, a family of outer membrane proteases that is widespread in gram-negative bacteria. While the physiological role of most omptins (such as E. coli OmpT) is unclear, Y. pestis Pla has a proven, very important role in the virulence of both bubonic and pneumonic plague by cleaving (activation of) human plasminogen. We are investigatng the high-resolution crystal structure of Pla inorder to gain information into the catalytic mechanism of omptins and the structural basis for substrate specificity. B. Structure of a full-length autotransporter. The autotransporter secretion mechanism is the most common mechanism for the secretion of virulence factors across the outer membrane (OM) from pathogenic Gram-negative bacteria. In addition, autotransporters have attracted biotechnological and biomedical interest for protein display on bacterial cell surfaces. Despite their importance, the mechanism by which passenger domains of autotransporters pass the OM is still unclear. The classical view is that the ¿-barrel domain provides the conduit through which the unfolded passenger moves, with the energy provided by vectorial folding of the ¿-strand-rich passenger on the extracellular side of the OM.