STRUCTURAL STUDIES OF THE 70 KDA SECB CHAPERONE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 SecB是一种细菌分子伴侣，是SEC分泌系统的关键组成部分。它不仅负责识别和维持处于延长的分泌能力状态的前蛋白，并将它们运送到外周膜上的输出装置，而且还可能作为一般的胞浆伴侣发挥作用。SecB在体外结合了大量未折叠的蛋白质序列，但在体内具有高度的选择性。识别背后的结构和能量机制尚不清楚，但人们认为SecB使用具有不同化学性质的多个结合亚基来促进对不同底物的特异性。由于功能同源物在所有形式的生命中都存在，SecB作为一个顺从的系统来详细探索所涉及的识别和结合过程。该方案的目的是对具有代表性的多肽底物的复合体中SecB的结构进行表征，并确定SecB配体识别和结合专一性的动力学、力学和热力学参数。

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. SecB is a bacterial molecular chaperone that is a critical component of the Sec secretion system. It is not only responsible for recognizing and maintaining preproteins in an extended, secretion-competent state and delivering them to the export apparatus at the peripheral membrane, but may also function as a general cytosolic chaperone. SecB binds a vast array of unfolded protein sequences in vitro, yet is highly selective in vivo. The structural and energetic mechanisms behind recognition are poorly understood, but it is believed SecB uses multiple binding subsites with different chemical properties to promote a specificity to diverse substrates. As functional homologs are found in all forms of life, SecB serves as an amenable system with which to explore in detail the recognition and binding processes involved. The objective of this proposal is to structurally characterize SecB in complex with representative peptide substrates and to define the dynamic, mechanistic and thermodynamic parameters underlying SecB-ligand recognition and binding specificity.