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.
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