Dcn1 functions as a scaffold-type E3 ligase for cullin neddylation

Kurz, T. , Chou, Y.-C., Willems, A. R., Meyer-Schaller, N., Hecht, M.-L., Tyers, M., Peter, M. and Sicheri, F. (2008) Dcn1 functions as a scaffold-type E3 ligase for cullin neddylation. Molecular Cell, 29(1), pp. 23-35. (doi: 10.1016/j.molcel.2007.12.012) (PMID:18206966)

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Abstract

Cullin-based E3 ubiquitin ligases are activated through modification of the cullin subunit with the ubiquitin-like protein Nedd8. Dcn1 regulates cullin neddylation and thus ubiquitin ligase activity. Here we describe the 1.9 Å X-ray crystal structure of yeast Dcn1 encompassing an N-terminal ubiquitin-binding (UBA) domain and a C-terminal domain of unique architecture, which we termed PONY domain. A conserved surface on Dcn1 is required for direct binding to cullins and for neddylation. The reciprocal binding site for Dcn1 on Cdc53 is located ∼18 Å from the site of neddylation. Dcn1 does not require cysteine residues for catalytic function, and directly interacts with the Nedd8 E2 Ubc12 on a surface that overlaps with the E1-binding site. We show that Dcn1 is necessary and sufficient for cullin neddylation in a purified recombinant system. Taken together, these data demonstrate that Dcn1 is a scaffold-like E3 ligase for cullin neddylation.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kurz, Dr Thimo
Authors: Kurz, T., Chou, Y.-C., Willems, A. R., Meyer-Schaller, N., Hecht, M.-L., Tyers, M., Peter, M., and Sicheri, F.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:Molecular Cell
Publisher:Elsevier (Cell Press)
ISSN:1097-2765
ISSN (Online):1097-4164
Published Online:17 January 2008

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