UNDERSTANDING SEC-FACILITATE PROTEIN TRANSLOCATION AND MEMBRANE INTEGRATION: NE

了解 SEC 促进蛋白质易位和膜整合：NE

• 批准号: 8364338
• 负责人: THOMAS F MILLER
• 金额: $ 0.11万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8364338
• 关键词: Address; Binding; Biochemical Genetics; Biomedical Research; Cellular Membrane; Data; Funding; Grant; High Performance Computing; Membrane; Molecular Motors; National Center for Research Resources; Peptides; Principal Investigator; Process; Protein Biosynthesis; Protein translocation; Regulation; Research; Research Infrastructure; Resolution; Resources; Source; United States National Institutes of Health; cost; response; simulation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. A critical step in protein biosynthesis involves either translocation across a cellular membrane or integration into a cellular membrane. Both processes proceed via the Sec translocon - a ubiquitous and highly conserved transmembrane channel. Recent structural studies offer high-resolution snapshots of the translocon, and a wealth of biochemical and genetic data reveal important interactions within the translocon; but many aspects of its mechanism and regulation remain unclear. We propose to address two central questions about the mechanism of Sec-facilitated protein translocation and membrane integration that are nearly impossible to resolve without the long-timescale simulations made possible by Anton. Specifically, these questions are: (1) What is the conformational response of the Sec translocon to the slow insertion of hydrophobic and hydrophilic peptide substrates? (2) Does the binding of molecular motors to the translocon induce conformational changes that are essential for protein translocation and membrane integration? We propose long-timescale simulation studies that will directly address these two fundamental questions.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 蛋白质生物合成的关键步骤包括跨细胞膜转位或整合到细胞膜中。这两个过程都是通过SEC转运子进行的，SEC转运子是一种普遍存在的高度保守的跨膜通道。最近的结构研究提供了转位基因的高分辨率快照，大量的生化和遗传数据揭示了转位基因内部的重要相互作用；但其机制和调控的许多方面仍不清楚。我们建议解决关于SEC促进的蛋白质转位和膜整合机制的两个核心问题，如果没有Anton提供的长时间尺度模拟，这些问题几乎是不可能解决的。具体地说，这些问题是：(1)SEC易位子对疏水性和亲水性多肽底物缓慢插入的构象反应是什么？(2)分子马达与易位子的结合是否会引起对蛋白质转运和膜整合至关重要的构象变化？我们建议进行长时间尺度的模拟研究，直接解决这两个基本问题。