STRUCTURAL STUDIES OF INTERACTIONS AMONG BCL-2 FAMILY PROTEINS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 基廷实验室的研究旨在了解人类Bcl-2家族蛋白之间相互作用特异性的决定因素。Bcl2蛋白调节细胞凋亡，已成为重要的抗癌药物靶点。我们正在研究来源于促凋亡蛋白BH3区的短α螺旋多肽与抗凋亡家族成员的结合。我们进行结合研究和结构研究，并将这些与计算方法相结合，以更好地理解序列如何决定相互作用的特异性。X射线结晶学研究是这项工作的关键组成部分，因为结构提供了对受体蛋白如何调整以结合一系列不同配体的见解。由于新的结构快照可以为多肽或小分子药物设计提供机会，这些研究对新疗法和诊断学的发展具有重要意义。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Research in the Keating lab aims to understand determinants of interaction specificity among human Bcl-2 family proteins. The Bcl-2 proteins regulate apoptotis and have emerged as important anti-cancer drug targets. We are studying the binding of short alpha-helical peptides derived from the BH3 region of pro-apoptotic Bcl-2 proteins to anti-apoptotic family members. We carry out binding studies and structural studies and combine these with computational methods to obtain a better understanding of how sequence determines interaction specificity. X-ray crystallographic studies are a key component of this work, as structure provides insights into how the receptor proteins can adjust to bind a range of different ligands. Because new structural snapshots can provide opportunities for peptide or small-molecule drug design, these studies have implications for the development of new therapeutics and diagnotics.