6ASY

BiP-ATP2

Summary for 6ASY

• Entry DOI: 10.2210/pdb6asy/pdb
• Descriptor: 78 kDa glucose-regulated protein, GLYCEROL, ADENOSINE-5'-TRIPHOSPHATE, ... (6 entities in total)
• Functional Keywords: hsp70s, chaperone
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 137945.28

Authors

Liu, Q.,Yang, J.,Zong, Y.,Columbus, L.,Zhou, L. (deposition date: 2017-08-26, release date: 2017-12-06, Last modification date: 2024-03-13)

Primary citation

Yang, J.,Zong, Y.,Su, J.,Li, H.,Zhu, H.,Columbus, L.,Zhou, L.,Liu, Q.
Conformation transitions of the polypeptide-binding pocket support an active substrate release from Hsp70s.
Nat Commun, 8:1201-1201, 2017

PubMed Abstract: Cellular protein homeostasis depends on heat shock proteins 70 kDa (Hsp70s), a class of ubiquitous and highly conserved molecular chaperone. Key to the chaperone activity is an ATP-induced allosteric regulation of polypeptide substrate binding and release. To illuminate the molecular mechanism of this allosteric coupling, here we present a novel crystal structure of an intact human BiP, an essential Hsp70 in ER, in an ATP-bound state. Strikingly, the polypeptide-binding pocket is completely closed, seemingly excluding any substrate binding. Our FRET, biochemical and EPR analysis suggests that this fully closed conformation is the major conformation for the ATP-bound state in solution, providing evidence for an active release of bound polypeptide substrates following ATP binding. The Hsp40 co-chaperone converts this fully closed conformation to an open conformation to initiate productive substrate binding. Taken together, this study provided a mechanistic understanding of the dynamic nature of the polypeptide-binding pocket in the Hsp70 chaperone cycle.

PubMed: 29084938
DOI: 10.1038/s41467-017-01310-z

Experimental method

X-RAY DIFFRACTION (1.85 Å)