MOLECULAR STRUCTURE OF BIOLOGICAL MOLECULES

基因组数据库中至少有25%的基因具有假定的跨膜螺旋，这一发现突显了膜蛋白的生物学重要性。然而，膜蛋白的结构很少，这在很大程度上是因为很难为研究创造一个可溶的、稳定的状态。我们建议探索膜蛋白结构测定的替代方法。我们已经成功地重新设计了磷蛋白，一种五聚体膜蛋白，导致了一种稳定的五聚体水溶性结构，在核磁共振中提供了远程NOE信号。我们将利用这种分子作为先导化合物来探索重组膜蛋白的稳定性和水溶度的原理。我们将通过核磁共振检查选定的标记的结构，并尝试和尝试结晶。作为重新设计的另一种选择，我们将考察新型表面活性剂--聚合物两亲化合物的性质，它比传统表面活性剂具有相当大的优势，并可能为核磁共振和/或结晶学提供一个新的方向。我们将使用溶液散射来测量膜的厚度和它们的双层脂类。我们将继续使用溶液散射来研究可溶性蛋白和膜蛋白的齐聚和折叠问题。

The biological importance of membrane proteins has been underscored by the discovery that at least 25% of all genes in genomic databases have putative transmembrane helices. Yet, there are few structure for membrane proteins, largely because it is hard to create a soluble, stable state for study. We propose to explore alternative methods for structure determination for membrane proteins. We have succeeded in a re-design of phospholamban, a pentameric membrane protein, leading to a stable, pentameric, water-soluble structure that gives long-range NOE signals in NMR. We will use this molecule as a lead compound to explore the principles of stability and aqueous solubility for re-engineering membrane proteins. We will examine the structure of selected signs by NMR and attempt and attempt crystallization. As an alternative to the use of re-design, we will examine the properties of new class of surfactant, polymeric amphiphiles, which has considerable advantages over conventional surfactants, and may provide a new direction for NMR and/or crystallography. We will use solution scattering to measure the thickness of membranes and bilayers of lipids from them. We will continue our use of solution scattering to examine issues of oligomerization and folding of soluble and membrane proteins.