TM INTERACTIONS IN MEMBRANE PROTEIN FOLDING AND FUNCTION

描述（由申请人提供）：跨膜螺旋之间的相互作用是膜蛋白结构的主要特征。了解指导这种相互作用的原则将阐明膜蛋白折叠，稳定性和寡聚体的形成。由于膜蛋白由超过20%的基因编码，并且是超过一半的药物的靶点，这样的理解将是有启发性和有用的。我们将致力于理解的图案和相互作用，引起跨膜螺旋（TM）的相互作用，稳定在生物膜中的蛋白质结构，并开始连接我们的理解生物功能。我们已经开发了一个多样化的工具包TM相互作用的研究，包括：（a）在胶束，双层和膜，（B）计算方法，（c）使用光谱和NMR的结构研究的遗传和生物化学测定。我们的方法将有几个主要部分：TM三聚体在HIV gp 41 TM和MHC li的研究;努力找到螺旋二聚化和信号之间的联系;相互作用的图案的研究; TM-TM计算方法的改进;和测试的原则和图案，可以确定在螺旋协会。

DESCRIPTION (provided by applicant): Interactions between transmembrane helices are a major feature of the architecture of membrane proteins. Understanding the principles that guide such interactions will illuminate membrane protein folding, stability, and oligomer formation. Since membrane proteins are coded by more than 20% of all genes and are the targets of more than half of all drugs, such an understanding will be both enlightening and useful. We will work towards understanding the motifs and interactions that give rise to transmembrane helix (TM) interactions that stabilize protein structures in biological membranes, and to begin to connect our understanding to biological functions. We have developed a diverse toolkit for the study of TM interactions, including: (a) genetic and biochemical assays in micelles, bilayers and membranes, (b) computational approaches, and (c) structural studies using optical spectroscopy and NMR. Our approach will have several major divisions: a study of TM trimers in HIV gp41 TMs and MHC li; an effort to find the link between helix dimerization and signaling; a study of interaction motifs; an improvement of TM-TM computational methods; and tests of the principles and motifs that can be identified in helix associations.