5xi9 | pdb_00005xi9
Solution structure for human HSP70 substrate binding domain
Structural highlights
Function[HS71A_HUMAN] In cooperation with other chaperones, Hsp70s stabilize preexistent proteins against aggregation and mediate the folding of newly translated polypeptides in the cytosol as well as within organelles. These chaperones participate in all these processes through their ability to recognize nonnative conformations of other proteins. They bind extended peptide segments with a net hydrophobic character exposed by polypeptides during translation and membrane translocation, or following stress-induced damage. In case of rotavirus A infection, serves as a post-attachment receptor for the virus to facilitate entry into the cell. Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation (PubMed:23973223).[1] [2] [3] Publication Abstract from PubMedThe stress-induced 70 kDa heat shock protein (Hsp70) functions as a molecular chaperone to maintain protein homeostasis. Hsp70 contains an N-terminal ATPase domain (NBD) and a C-terminal substrate-binding domain (SBD). The SBD is divided into the beta subdomain containing the substrate-binding site (betaSBD) and the alpha-helical subdomain (alphaLid) that covers the betaSBD. In this report, the solution structures of two different forms of the SBD from human Hsp70 were solved. One structure shows the alphaLid bound to the substrate-binding site intramolecularly, whereas this intramolecular binding mode is absent in the other structure solved. Structural comparison of the two SBDs from Hsp70 revealed that client-peptide binding rearranges residues at the interdomain contact site, which impairs interdomain contact between the SBD and the NBD. Peptide binding also disrupted the inter-subdomain interaction connecting the alphaLid to the betaSBD, which allows the binding of the alphaLid to the NBD. The results provide a mechanism for interdomain communication upon substrate binding from the SBD to the NBD via the lynchpin site in the betaSBD of human Hsp70. In comparison to the bacterial ortholog, DnaK, some remarkable differences in the allosteric signal propagation among residues within the Hsp70 SBD exist. Substrate Binding Switches the Conformation at the Lynchpin Site in the Substrate-Binding Domain of Human Hsp70 to Enable Allosteric Interdomain Communication.,Umehara K, Hoshikawa M, Tochio N, Tate SI Molecules. 2018 Feb 27;23(3). pii: molecules23030528. doi:, 10.3390/molecules23030528. PMID:29495458[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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