ALLOSTERY AND INTERDOMAIN ORIENTATION IN THE DNAK MOLECULAR CHAPERONE

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。 Hsp70家族成员的伴侣活性依赖于其两个亚域各自的变构控制，该控制由另一个亚域执行。ATP(而不是ADP)与N-末端结构域的结合降低了CT端结构域与其肽底物的结合亲和力，而肽底物与C-末端结构域的结合则加速了N-末端结构域将ATP水解为ADP。不同区域的可靠原子分辨结构已经得到解决，但区域间通信的细节，甚至区域的相对取向，仍然存在争议。目前还不清楚现有的晶体结构和核磁共振数据代表了哪种状态(ATP结合，ADP结合，没有我们的肽底物)。我们建议使用小角X射线散射来测试特定的域间定向模型，并以此为基础建立一个有用的域间通信模型。

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. Chaperone activity of the Hsp70 family members depends on allosteric control of each of its two sub-domains, which control is exercised by the other sub-domain. Binding of ATP (but not ADP) to the N-terminal domain lowers binding affinity of the Cterminal domain for its peptide substrates, while binding of peptide substrates to the C-terminal domain accelerates the hydrolysis of ATP to ADP by the N-terminal domain. Reliable atomic resolution structures of the separate domains have been solved, but the details of interdomain communication, even the relative orientation of the domains, remains controversial. It is unclear which state (ATP-bound, ADP-bound, with our without peptide substrate) is represented by available crystal structures and NMR data. We propose to use small angle x-ray scattering to test specific models of interdomain orientation and use this as the basis for a useful model of interdomain communication.