4JN4

Allosteric opening of the polypeptide-binding site when an Hsp70 binds ATP

Summary for 4JN4

• Entry DOI: 10.2210/pdb4jn4/pdb
• Descriptor: Chaperone protein DnaK, MAGNESIUM ION, ADENOSINE-5'-TRIPHOSPHATE, ... (6 entities in total)
• Functional Keywords: dnak, chaperone, 70kda heat shock protein (hsp70), single-wavelength anomalous diffraction (sad), native structure determination, multiple crystals
• Biological source: Escherichia coli
• Cellular location: Cytoplasm: P0A6Y8
• Total number of polymer chains: 2
• Total formula weight: 134274.73

Authors

Qi, R.,Sarbeng, E.B.,Liu, Q.,Le, K.Q.,Xu, X.,Xu, H.,Yang, J.,Wong, J.L.,Vorvis, C.,Hendrickson, W.A.,Zhou, L.,Liu, Q. (deposition date: 2013-03-14, release date: 2013-05-29, Last modification date: 2024-02-28)

Primary citation

Qi, R.,Sarbeng, E.B.,Liu, Q.,Le, K.Q.,Xu, X.,Xu, H.,Yang, J.,Wong, J.L.,Vorvis, C.,Hendrickson, W.A.,Zhou, L.,Liu, Q.
Allosteric opening of the polypeptide-binding site when an Hsp70 binds ATP.
Nat.Struct.Mol.Biol., 20:900-907, 2013

PubMed Abstract: The 70-kilodalton (kDa) heat-shock proteins (Hsp70s) are ubiquitous molecular chaperones essential for cellular protein folding and proteostasis. Each Hsp70 has two functional domains: a nucleotide-binding domain (NBD), which binds and hydrolyzes ATP, and a substrate-binding domain (SBD), which binds extended polypeptides. NBD and SBD interact little when in the presence of ADP; however, ATP binding allosterically couples the polypeptide- and ATP-binding sites. ATP binding promotes polypeptide release; polypeptide rebinding stimulates ATP hydrolysis. This allosteric coupling is poorly understood. Here we present the crystal structure of an intact ATP-bound Hsp70 from Escherichia coli at 1.96-Å resolution. The ATP-bound NBD adopts a unique conformation, forming extensive interfaces with an SBD that has changed radically, having its α-helical lid displaced and the polypeptide-binding channel of its β-subdomain restructured. These conformational changes, together with our biochemical assays, provide a structural explanation for allosteric coupling in Hsp70 activity.

PubMed: 23708608
DOI: 10.1038/nsmb.2583

Experimental method

X-RAY DIFFRACTION (2.3 Å)