<> "The repository administrator has not yet configured an RDF license."^^ . <> . . . "Binding of a small molecule at a protein-protein interface regulates the chaperone activity of Hsp70-Hsp40"^^ . "Heat shock protein 70 (Hsp70) is a highly conserved molecular chaperone that plays multiple roles in protein homeostasis. In these various tasks, the activity of Hsp70 is shaped by interactions with co-chaperones, such as Hsp40. The Hsp40 family of co-chaperones binds to Hsp70 through a conserved J-domain, and these factors stimulate ATPase and protein-folding activity. Using chemical screens, we identified a compound, 115-7c, which acts as an artificial co-chaperone for Hsp70. Specifically, the activities of 115-7c mirrored those of a Hsp40; the compound stimulated the ATPase and protein-folding activities of a prokaryotic Hsp70 (DnaK) and partially compensated for a Hsp40 loss-of-function mutation in yeast. Consistent with these observations, NMR and mutagenesis studies indicate that the binding site for 115-7c is adjacent to a region on DnaK that is required for J-domain-mediated stimulation. Interestingly, we found that 115-7c and the Hsp40 do not compete for binding but act in concert. Using this information, we introduced additional steric bulk to 115-7c and converted it into an inhibitor. Thus, these chemical probes either promote or inhibit chaperone functions by regulating Hsp70-Hsp40 complex assembly at a native protein-protein interface. This unexpected mechanism may provide new avenues for exploring how chaperones and co-chaperones cooperate to shape protein homeostasis. © 2010 American Chemical Society."^^ . "2010-06-18" . . "5" . "6" . . "ACS Chemical Biology"^^ . . . "15548929" . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . "GM"^^ . "Walter"^^ . "GM Walter"^^ . . "P"^^ . "Ung"^^ . "P Ung"^^ . . "HA"^^ . "Carlson"^^ . "HA Carlson"^^ . . "EB"^^ . "Bertelsen"^^ . "EB Bertelsen"^^ . . "ERP"^^ . "Zuiderweg"^^ . "ERP Zuiderweg"^^ . . "JE"^^ . "Gestwicki"^^ . "JE Gestwicki"^^ . . "JL"^^ . "Brodsky"^^ . "JL Brodsky"^^ . . "P"^^ . "Wipf"^^ . "P Wipf"^^ . . "L"^^ . "Chang"^^ . "L Chang"^^ . . "S"^^ . "Wisén"^^ . "S Wisén"^^ . . "AD"^^ . "Thompson"^^ . "AD Thompson"^^ . . "S"^^ . "Patury"^^ . "S Patury"^^ . . "CG"^^ . "Evans"^^ . "CG Evans"^^ . . . . . . "Binding of a small molecule at a protein-protein interface regulates the chaperone activity of Hsp70-Hsp40 (Plain Text)"^^ . . . "licence.txt"^^ . . . "Binding of a small molecule at a protein-protein interface regulates the chaperone activity of Hsp70-Hsp40 (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #18794 \n\nBinding of a small molecule at a protein-protein interface regulates the chaperone activity of Hsp70-Hsp40\n\n" . "text/html" . .