3dqv

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3dqv, resolution 3.00Å ()
Ligands:
Non-Standard Residues:
Gene: NEDD8 (Homo sapiens), CUL5, VACM1 (Homo sapiens), RBX1, RNF75, ROC1 (Homo sapiens)
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Contents

Structural Insights into NEDD8 Activation of Cullin-RING Ligases: Conformational Control of Conjugation

Publication Abstract from PubMed

Cullin-RING ligases (CRLs) comprise the largest ubiquitin E3 subclass, in which a central cullin subunit links a substrate-binding adaptor with an E2-binding RING. Covalent attachment of the ubiquitin-like protein NEDD8 to a conserved C-terminal domain (ctd) lysine stimulates CRL ubiquitination activity and prevents binding of the inhibitor CAND1. Here we report striking conformational rearrangements in the crystal structure of NEDD8~Cul5(ctd)-Rbx1 and SAXS analysis of NEDD8~Cul1(ctd)-Rbx1 relative to their unmodified counterparts. In NEDD8ylated CRL structures, the cullin WHB and Rbx1 RING subdomains are dramatically reoriented, eliminating a CAND1-binding site and imparting multiple potential catalytic geometries to an associated E2. Biochemical analyses indicate that the structural malleability is important for both CRL NEDD8ylation and subsequent ubiquitination activities. Thus, our results point to a conformational control of CRL activity, with ligation of NEDD8 shifting equilibria to disfavor inactive CAND1-bound closed architectures, and favor dynamic, open forms that promote polyubiquitination.

Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation., Duda DM, Borg LA, Scott DC, Hunt HW, Hammel M, Schulman BA, Cell. 2008 Sep 19;134(6):995-1006. PMID:18805092

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

3dqv is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

See Also

Reference

  • Duda DM, Borg LA, Scott DC, Hunt HW, Hammel M, Schulman BA. Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation. Cell. 2008 Sep 19;134(6):995-1006. PMID:18805092 doi:http://dx.doi.org/10.1016/j.cell.2008.07.022

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