2f42

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(New page: 200px<br /><applet load="2f42" size="350" color="white" frame="true" align="right" spinBox="true" caption="2f42, resolution 2.50&Aring;" /> '''dimerization and U-b...)
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Revision as of 17:27, 29 January 2008


2f42, resolution 2.50Å

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dimerization and U-box domains of Zebrafish C-terminal of HSP70 interacting protein

Overview

The heat-shock proteins Hsp70 and Hsp90 play a crucial role in regulating, protein quality control both by refolding and by preventing the, aggregation of misfolded proteins. It has recently been shown that Hsp70, and Hsp90 act not only in protein refolding but also cooperate with the C, terminus of Hsp70 interacting protein (CHIP), a multidomain ubiquitin, ligase, to mediate the degradation of unfolded proteins. We present the, crystal structure of the helical linker domain and U-box domain of, zebrafish CHIP (DrCHIP-HU). The structure of DrCHIP-HU shows a symmetric, homodimer. The conformation of the helical linker domains and the relative, positions of the helical and U-box domains differ substantially in, DrCHIP-HU from those in a recently published structure of an asymmetric, dimer of mammalian (mouse) CHIP. We used an in vitro ubiquitination assay, to identify residues, located on two long loops and a central alpha helix, of the CHIP U-box domain, that are important for interacting with the, ubiquitin-conjugating enzyme UbcH5b. In addition, we used NMR spectroscopy, to define a complementary interaction surface located on the N-terminal, alpha helix and the L4 and L7 loops of UbcH5b. Our results provide, insights into conformational variability in the domain arrangement of CHIP, and into U-box-mediated recruitment of UbcH5b for the ubiquitination of, Hsp70 and Hsp90 substrates.

About this Structure

2F42 is a Single protein structure of sequence from Danio rerio with as ligand. Full crystallographic information is available from OCA.

Reference

Structure and interactions of the helical and U-box domains of CHIP, the C terminus of HSP70 interacting protein., Xu Z, Devlin KI, Ford MG, Nix JC, Qin J, Misra S, Biochemistry. 2006 Apr 18;45(15):4749-59. PMID:16605243

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