ALLOSTERY AND INTERDOMAIN ORIENTATION IN THE DNAK MOLECULAR CHAPERONE

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 Hsp 70家族成员的伴侣活性取决于其两个亚结构域中的每一个的变构控制，该控制由另一个亚结构域行使。ATP（而非ADP）与N-末端结构域的结合降低了C-末端结构域对其肽底物的结合亲和力，而肽底物与C-末端结构域的结合加速了N-末端结构域将ATP水解为ADP。可靠的原子分辨率结构的独立域已经解决，但域间通信的细节，甚至域的相对取向，仍然存在争议。目前还不清楚哪种状态（ATP结合，ADP结合，有或没有肽底物）由可用的晶体结构和NMR数据表示。我们建议使用小角度X射线散射来测试特定的模型域间取向，并使用此作为域间通信的一个有用的模型的基础。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.