STRUCTURAL STUDIES OF THE 70 KDA SECB CHAPERONE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 SecB是细菌分子伴侣，是Sec分泌系统的关键组分。它不仅负责识别和维持前蛋白在一个扩展的，有分泌能力的状态，并将其提供给输出装置在外周膜，但也可以作为一个一般的胞质伴侣。SecB在体外结合大量未折叠的蛋白质序列，但在体内具有高度选择性。识别背后的结构和能量机制知之甚少，但据信SecB使用具有不同化学性质的多个结合亚位点来促进对不同底物的特异性。 由于在所有形式的生命中都发现了功能同源物，SecB作为一个顺从的系统，可以详细探索所涉及的识别和结合过程。该提案的目的是在结构上表征SecB与代表性肽底物的复合物，并定义SecB-配体识别和结合特异性的动力学，机械学和热力学参数。

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.