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PDBsum entry 2c2l
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References listed in PDB file
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Key reference
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Title
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Chaperoned ubiquitylation--Crystal structures of the chip u box e3 ubiquitin ligase and a chip-Ubc13-Uev1a complex.
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Authors
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M.Zhang,
M.Windheim,
S.M.Roe,
M.Peggie,
P.Cohen,
C.Prodromou,
L.H.Pearl.
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Ref.
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Mol Cell, 2005,
20,
525-538.
[DOI no: ]
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PubMed id
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Abstract
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CHIP is a dimeric U box E3 ubiquitin ligase that binds Hsp90 and/or Hsp70 via
its TPR-domain, facilitating ubiquitylation of chaperone bound client proteins.
We have determined the crystal structure of CHIP bound to an Hsp90 C-terminal
decapeptide. The structure explains how CHIP associates with either chaperone
type and reveals an unusual asymmetric homodimer in which the protomers adopt
radically different conformations. Additionally, we identified CHIP as a
functional partner of Ubc13-Uev1a in formation of Lys63-linked polyubiquitin
chains, extending CHIP's roles into ubiquitin regulation as well as targeted
destruction. The structure of Ubc13-Uev1a bound to the CHIP U box domain defines
the basis for selective cooperation of CHIP with specific ubiquitin-conjugating
enzymes. Remarkably, the asymmetric arrangement of the TPR domains in the CHIP
dimer occludes one Ubc binding site, so that CHIP operates with half-of-sites
activity, providing an elegant means for coupling a dimeric chaperone to a
single ubiquitylation system.
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Figure 2.
Figure 2. Architecture of the CHIP Homodimer
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Figure 3.
Figure 3. Asymmetric Disposition of TPR Domains
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The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(2005,
20,
525-538)
copyright 2005.
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