UNDERSTANDING SEC-FACILITATE PROTEIN TRANSLOCATION AND MEMBRANE INTEGRATION: NE

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 蛋白质生物合成中的关键步骤涉及跨细胞膜转运或整合到细胞膜中。这两个过程都是通过Sec转座子进行的，Sec转座子是一种普遍存在且高度保守的跨膜通道。最近的结构研究提供了高分辨率的快照的易位子，和丰富的生化和遗传数据揭示了重要的易位子内的相互作用，但其机制和调节的许多方面仍然不清楚。 我们建议解决两个中心问题的机制，SEC促进蛋白质易位和膜整合，这几乎是不可能解决的，没有长时间尺度的模拟可能由安东。 具体而言，这些问题是：（1）什么是构象的响应的Sec转座的疏水性和亲水性肽底物的缓慢插入？(2)分子马达与易位子的结合是否会引起蛋白质转运和膜整合所必需的构象变化？ 我们提出了长期的模拟研究，将直接解决这两个基本问题。

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.