2C2L

Crystal structure of the CHIP U-box E3 ubiquitin ligase

Summary for 2C2L

• Entry DOI: 10.2210/pdb2c2l/pdb
• Descriptor: CARBOXY TERMINUS OF HSP70-INTERACTING PROTEIN, HSP90, SULFATE ION, ... (5 entities in total)
• Functional Keywords: chaperone, e3 ligase, ubiquitinylation, tpr, heat-shock protein complex
• Biological source: MUS MUSCULUS (MOUSE); More
• Total number of polymer chains: 8
• Total formula weight: 136151.31

Authors

Zhang, M.,Roe, S.M.,Pearl, L.H. (deposition date: 2005-09-29, release date: 2005-11-23, Last modification date: 2024-05-01)

Primary citation

Zhang, M.,Windheim, M.,Roe, S.M.,Peggie, M.,Cohen, P.,Prodromou, C.,Pearl, L.H.
Chaperoned Ubiquitylation-Crystal Structures of the Chip U Box E3 Ubiquitin Ligase and a Chip-Ubc13-Uev1A Complex
Mol.Cell, 20:525-, 2005

PubMed Abstract: 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.

PubMed: 16307917
DOI: 10.1016/J.MOLCEL.2005.09.023

Experimental method

X-RAY DIFFRACTION (3.3 Å)