ASSESSING E2~UBIQUITIN DYNAMICS USING SMALL ANGLE X-RAY SCATTERING

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 泛素化是最保守的分子修饰之一。8.6- kDa蛋白质的附着可以采取多种形式，并作为蛋白质命运的许多不同信号。Ub与底物的共价连接通过以E2泛素缀合酶为中心的多酶过程进行。虽然了解不多，E2~Ub结合物似乎影响E3连接酶、底物和连接类型特异性。本文通过分析E2~Ub结合物结构动力学的差异来探讨这一问题。NMR分析显示E2~Ub缀合物的柔性。此外，域间运动的程度和模式似乎在很大程度上依赖于E2。SAXS是NMR研究溶液中蛋白质的有力替代品。快速访问SAXS需要证实这一假设即将出版。

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. Ubiquitination is among the most conserved of molecular modifications. Attachment of the 8.6- kDa protein can take many forms and serve as many distinct signals for protein fate. The covalent attachment of Ub to a substrate proceeds via a multi-enzyme process centered around an E2 ubiquitin conjugating enzyme. Though poorly understood, the E2~Ub conjugate appears to influence E3 ligase, substrate, and linkage type specificities. This proposal approaches this issue by analyzing differences in structural dynamics among E2~Ub conjugates. NMR analysis has revealed flexibility in the E2~Ub conjugate. Additionally, the degree and pattern of interdomain movements appears to be largely E2 dependent. SAXS is a powerful alternative to NMR for studying proteins in solution. Rapid access to SAXS is required to corroborate this hypothesis for impending publication.