1s3x

From Proteopedia

Revision as of 14:52, 15 February 2008

The crystal structure of the human Hsp70 ATPase domain

Overview

BACKGROUND: The 70 kDa heat shock proteins (Hsp70) are a family of, molecular chaperones, which promote protein folding and participate in, many cellular functions. The Hsp70 chaperones are composed of two major, domains. The N-terminal ATPase domain binds to and hydrolyzes ATP, whereas, the C-terminal domain is required for polypeptide binding. Cooperation of, both domains is needed for protein folding. The crystal structure of, bovine Hsc70 ATPase domain (bATPase) has been determined and, more, recently, the crystal structure of the peptide-binding domain of a related, chaperone, DnaK, in complex with peptide substrate has been obtained. The, molecular chaperone activity and conformational switch are functionally, linked with ATP hydrolysis. A high-resolution structure of the ATPase, domain is required to provide an understanding of the mechanism of ATP, hydrolysis and how it affects communication between C- and N-terminal, domains. RESULTS: The crystal structure of the human Hsp70 ATPase domain, (hATPase) has been determined and refined at 1. 84 A, using synchrotron, radiation at 120K. Two calcium sites were identified: the first calcium, binds within the catalytic pocket, bridging ADP and inorganic phosphate, and the second calcium is tightly coordinated on the protein surface by, Glu231, Asp232 and the carbonyl of His227. Overall, the structure of, hATPase is similar to bATPase. Differences between them are found in the, loops, the sites of amino acid substitution and the calcium-binding sites., Human Hsp70 chaperone is phosphorylated in vitro in the presence of, divalent ions, calcium being the most effective. CONCLUSIONS: The, structural similarity of hATPase and bATPase and the sequence similarity, within the Hsp70 chaperone family suggest a universal mechanism of ATP, hydrolysis among all Hsp70 molecular chaperones. Two calcium ions have, been found in the hATPase structure. One corresponds to the magnesium site, in bATPase and appears to be important for ATP hydrolysis and in vitro, phosphorylation. Local changes in protein structure as a result of calcium, binding may facilitate phosphorylation. A small, but significant, movement, of metal ions and sidechains could position catalytically important, threonine residues for phosphorylation. The second calcium site represents, a new calcium-binding motif that can play a role in the stabilization of, protein structure. We discuss how the information about catalytic events, in the active site could be transmitted to the peptide-binding domain.

About this Structure

1S3X is a Single protein structure of sequence from Homo sapiens with , , and as ligands. Full crystallographic information is available from OCA.

Reference

Human Hsp70 molecular chaperone binds two calcium ions within the ATPase domain., Sriram M, Osipiuk J, Freeman B, Morimoto R, Joachimiak A, Structure. 1997 Mar 15;5(3):403-14. PMID:9083109

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