STRUCTURE AND FOLDING OF INTEGRAL MEMBRANE PROTEINS

描述：（来自申请人的摘要）大约30%到40%的人 预期人蛋白质是整合的膜蛋白。虽然 编码这些蛋白质的所有基因的序列将在不久的将来被知道。 未来，只有少数几个的三维结构已经被 解决了从序列预测结构对于膜可能更简单 蛋白质比可溶性蛋白质，因为有序的流体结构， 脂双层限制膜蛋白的折叠。主要限制 许多相关的基本力量， 膜蛋白的折叠是未知的。该项目的目标是 研究膜蛋白的结构和折叠， 膜蛋白A（OmpA）。大肠杆菌作为模型。具体而言， 该通道蛋白的跨膜结构域将通过NMR解析 谱基本的脂质-蛋白质和蛋白质-蛋白质相互作用将是 决定了引导这个膜的折叠，并通过延伸， proteins.不同的脂质如何调节折叠， 将研究C末端结构域对OmpA折叠的贡献。 最后，候选周质伴侣蛋白的作用将是 考察由于膜蛋白的折叠不是一个既定的领域， 这项研究的一个重要组成部分是继续开发新的 适用于膜中间体表征的方法 蛋白质折叠

Description: (From the applicant's abstract) About 30 to 40 percent of all human proteins are expected to be integral membrane proteins. Although the sequences of all genes coding for these proteins will be known in the very near future, the three-dimensional structures of only a few of them have been solved. Structure prediction from sequences may be simpler for membrane proteins than for soluble proteins because the ordered fluid structure of the lipid bilayer constrains the folding of membrane proteins. The major limitation of this approach is that many of the relevant fundamental forces that govern membrane protein folding are not yet known. The goal of this project is to study the structure and folding of membrane proteins by using the outer membrane protein A (OmpA) of E. coli as a model. Specifically, the structure of the transmembrane domain of this channel protein will be solved by NMR spectroscopy. Elementary lipid-protein and protein-protein interactions will be determined that direct the folding of this and, by extension, other membrane proteins. How different lipids modulate folding and to what extent the C-terminal domain contributes to the folding of OmpA will be investigated. Finally, the role of a candidate periplasmic chaperone protein will be examined. Since folding of membrane proteins is not an established field, an important component of the proposed research is to continue to develop new methods that are suitable for the characterization of intermediates of membrane protein folding.