AR COBRE: PROTEIN TARGETING

AR COBRE：蛋白质靶向

• 批准号: 7381117
• 负责人: ROBYN GOFORTH
• 金额: $ 34.7万
• 依托单位: UNIVERSITY OF ARKANSAS AT FAYETTEVILLE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381117
• 关键词: AR; COBRE; PROTEIN; TARGETING

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. Signal recognition particles (SRPs) and their receptors function in every domain of life. They are components of an elaborate protein targeting system that delivers newly synthesized proteins to transporters (protein translocases) present in three different membrane systems; the bacterial cytoplasmic membrane, the endoplasmic reticulum, and the chloroplast thylakoid membrane. Malfunction of the SRP targeting/translocation system in humans is implicated in idiopathic inflammatory myopathies, diabetes mellitus, and colon cancer. In bacteria, SRP function is central to the success of bacterial pathogens. Complexities of SRP targeting continue to slow a detailed mechanistic model for how SRP targets and transfers proteins to translocation machinery located in the target membrane. Unique structural and functional features of the more recently discovered chloroplast SRP provide an unprecedented opportunity to examine the SRP targeting mechanism using tools and assays not available or not easily applied to other SRP-based targeting models. A transdisciplinary team led by Goforth and under the mentorship of Henry will apply advanced proteomics and protein structure analysis with more traditional molecular and biochemical approaches in order to (1) identify protein interactions between components of a SRP/receptor/translocase complex, (2) determine the structure of proteins critical for SRP to communicate with receptor and translocase, and (3) determine the function of specific protein/protein interactions in assays that reconstitute each step of the targeting/translocation mechanism. Completion of the proposed work will provide understanding of interactions that (i) are needed for targeting components to engage appropriate and available translocation machinery, (ii) regulate substrate release from SRP to the translocase, and (iii) control release of targeting components from the translocase. Our resulsts will broadly impact our understanding of the molecular machines that function in protein targeting and insertion. Moreover, insight gained through this transdisciplinary approach will provide needed comparative information to identify common mechanistic principals of SRP-based targeting. It is these common features that undoubtedly ensure faithful protein targeting and insertion despite evolutionary forces that have altered the SRP targeting/insertion machinery for efficient operation in a diverse array of organisms and cellular environments.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。信号识别颗粒 (SRP) 及其受体在生命的各个领域发挥作用。它们是精心设计的蛋白质靶向系统的组成部分，该系统将新合成的蛋白质递送至存在于三种不同膜系统中的转运蛋白（蛋白质转位酶）；细菌细胞质膜、内质网和叶绿体类囊体膜。人类 SRP 靶向/易位系统的故障与特发性炎症性肌病、糖尿病和结肠癌有关。在细菌中，SRP 功能对于细菌病原体的成功至关重要。 SRP 靶向的复杂性继续减慢 SRP 如何靶向并将蛋白质转移到位于靶膜中的易位机制的详细机制模型。最近发现的叶绿体 SRP 的独特结构和功能特征提供了前所未有的机会，可以使用其他基于 SRP 的靶向模型不可用或不易应用的工具和测定来检查 SRP 靶向机制。 由 Goforth 领导并在 Henry 指导下的跨学科团队将采用更传统的分子和生化方法来应用先进的蛋白质组学和蛋白质结构分析，以便 (1) 识别 SRP/受体/转位酶复合物成分之间的蛋白质相互作用，(2) 确定对 SRP 与受体和转位酶通讯至关重要的蛋白质结构，以及 (3) 确定特定蛋白质/蛋白质相互作用的功能 在重建靶向/易位机制的每个步骤的测定中。完成拟议的工作将有助于理解以下相互作用：(i) 靶向成分需要参与适当且可用的易位机制，(ii) 调节从 SRP 到转位酶的底物释放，以及 (iii) 控制靶向成分从转位酶的释放。我们的结果将广泛影响我们对蛋白质靶向和插入分子机器的理解。此外，通过这种跨学科方法获得的见解将提供所需的比较信息，以确定基于 SRP 的靶向的共同机制原理。尽管进化力量已经改变了 SRP 靶向/插入机制，以便在多种生物体和细胞环境中高效运行，但这些共同特征无疑确保了忠实的蛋白质靶向和插入。