2akp
From Proteopedia
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Hsp90 Delta24-N210 mutant
Overview
The molecular chaperone Hsp90 is required for the folding and activation, of a large number of substrate proteins. These are involved in essential, cellular processes ranging from signal transduction to viral replication., For the activation of its substrates, Hsp90 binds and hydrolyzes ATP, which is the key driving force for conformational conversions within the, dimeric chaperone. Dimerization of Hsp90 is mediated by a C-terminal, dimerization site. In addition, there is a transient ATP-induced, dimerization of the two N-terminal ATP-binding domains. The resulting, ring-like structure is thought to be the ATPase-active conformation. Hsp90, is a slow ATPase with a turnover number of 1 ATP/min for the yeast, protein. A key question for understanding the molecular mechanism of Hsp90, is how ATP hydrolysis is regulated and linked to conformational changes., In this study, we analyzed the activation process structurally and, biochemically with a view to identify the conformational limitations of, the ATPase reaction cycle. We showed that the first 24 amino acids, stabilize the N-terminal domain in a rigid state. Their removal confers, flexibility specifically to the region between amino acids 98 and 120., Most surprisingly, the deletion of this structure results in the complete, loss of ATPase activity and in increased N-terminal dimerization., Complementation assays using heterodimeric Hsp90 show that this rigid lid, acts as an intrinsic kinetic inhibitor of the Hsp90 ATPase cycle, preventing N-terminal dimerization in the ground state. On the other hand, this structure acts, in concert with the 24 N-terminal amino acids of the, other N-terminal domain, to form an activated ATPase and thus regulates, the turnover number of Hsp90.
About this Structure
2AKP is a Single protein structure of sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.
Reference
Intrinsic inhibition of the Hsp90 ATPase activity., Richter K, Moser S, Hagn F, Friedrich R, Hainzl O, Heller M, Schlee S, Kessler H, Reinstein J, Buchner J, J Biol Chem. 2006 Apr 21;281(16):11301-11. Epub 2006 Feb 6. PMID:16461354
Page seeded by OCA on Wed Nov 21 08:11:27 2007
