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. Author manuscript; available in PMC: 2015 May 19.
Published in final edited form as: Trends Biochem Sci. 2009 Apr 7;34(5):230–233. doi: 10.1016/j.tibs.2008.12.009

Figure 1.

Figure 1

(a) Hsp70 polypeptide binding and release is regulated through cycles of ATP hydrolysis and exchange. Protein misfolding is managed, in part, through the action of Hsp70 molecular chaperones in coordination with various cellular cofactors. Initially, a non-native polypeptide is bound by an Hsp40 co-chaperone (light blue). (b) The Hsp40 J-domain then binds Hsp70 (blue-green) in an ATP-bound state. (c) J-domain-stimulated ATP hydrolysis in the nucleotide-binding domain (NBD) induces a conformational shift in the Hsp70 substrate-binding domain (SBD), increasing affinity for the non-native polypeptide that is released from the Hsp40. Additional cofactors such as the E3 ubiquitin ligase CHIP (brown) with a ubiquitin-conjugating E2 (blue) can bind to Hsp70 and the non-native polypeptide, targeting the substrate for degradation by the ubiquitin-proteasome system (Poly-Ub). (d) Nucleotide exchange factors (NEFs) such as the Hsp110s (green) replace the ADP with ATP, releasing the polypeptide from Hsp70. (e) If the polypeptide remains in a non-native conformation, the cycle can be repeated until folding is complete.