Organization and Function of a Type II Secretion Complex

II 型分泌复合物的组织和功能

• 批准号: 6706891
• 负责人: Maria B Sandkvist
• 金额: --
• 依托单位: AMERICAN NATIONAL RED CROSS
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6706891
• 关键词: Vibrio cholerae; adenosine triphosphate; biological transport; cholera toxin; immunofluorescence technique; membrane transport proteins; protein binding; protein signal sequence; protein structure; protein transport

DESCRIPTION (provided by applicant): The type II secretion pathway is widely distributed among Gram-negative pathogens where it is responsible for extracellular secretion of toxins and degradative enzymes. At least 12 gene products located in both the cytoplasmic and outer membrane collectively comprise the type II secretion apparatus, which is specifically required for the translocation of secreted proteins from the periplasm to the extracellular milieu. This pathway is highly specific. It distinguishes secreted proteins from resident periplasmic proteins and discriminates between its own secreted proteins and those introduced from closely related species. In addition, secretion through this pathway differs from most other membrane transport systems in that its substrates consist of folded proteins. The objective of this proposal is to characterize the mechanism of type II secretion at the molecular level. The studies will utilize Vibrio cholerae and will specifically examine the secretion of cholera toxin (CT), as well as other proteins that utilize the type II pathway. CT provides an excellent model protein for these studies since its structure and function as well as its folding and assembly pathway are very well characterized. Specifically, we will test the hypotheses that: 1) Molecules secreted by the type II system encode information critical to their secretion within their tertiary structure, 2) the type II complex spans both membranes and components involved in connecting the outer membrane secretion pore with the cytoplasmic membrane regulate secretion by transducing energy to the secretion pore or by regulating its opening, 3) the secretion apparatus is localized to the poles or septum where the peptidoglycan undergoes rearrangements and/or where the pore size is atypical to allow for secretion of folded proteins.

描述（由申请人提供）：II 型分泌途径广泛存在 分布于革兰氏阴性病原体中，负责 细胞外分泌毒素和降解酶。至少12个基因 位于细胞质和外膜的产物统称 包括 II 型分泌装置，这是特别需要的 分泌蛋白从周质转移到细胞外 环境。该途径具有高度特异性。它区分分泌蛋白 来自常驻周质蛋白并区分其自身分泌的 蛋白质和从密切相关的物种引入的蛋白质。此外， 通过该途径的分泌不同于大多数其他膜运输 系统，因为它的底物由折叠蛋白质组成。 该提案的目的是描述 II 类机制的特征 分子水平的分泌。这些研究将利用霍乱弧菌和 将专门检查霍乱毒素（CT）以及其他毒素的分泌情况 利用 II 型途径的蛋白质。 CT提供了一个很好的模型 蛋白质用于这些研究，因为其结构和功能以及其 折叠和组装路径的特征非常明确。具体来说，我们将 检验以下假设： 1) II 型系统编码的分子分泌 对它们在三级结构中的分泌至关重要的信息，2) II 型复合体跨越膜和参与连接的组件 外膜分泌孔与细胞质膜调节分泌 通过将能量传导至分泌孔或调节其开口，3) 分泌器位于极或隔膜处 肽聚糖发生重排和/或孔径不典型 以允许折叠蛋白质的分泌。