Direct interactions between NEDD8 and ubiquitin E2 conjugating enzymes upregulate cullin-based E3 ligase activity

Eri Sakata; Yoshiki Yamaguchi; Yasuhiro Miyauchi; Kazuhiro Iwai; Tomoki Chiba; Yasushi Saeki; Noriyuki Matsuda; Keiji Tanaka; Koichi Kato

doi:10.1038/nsmb1191

Direct interactions between NEDD8 and ubiquitin E2 conjugating enzymes upregulate cullin-based E3 ligase activity

Nat Struct Mol Biol. 2007 Feb;14(2):167-8. doi: 10.1038/nsmb1191. Epub 2007 Jan 7.

Authors

Eri Sakata¹, Yoshiki Yamaguchi, Yasuhiro Miyauchi, Kazuhiro Iwai, Tomoki Chiba, Yasushi Saeki, Noriyuki Matsuda, Keiji Tanaka, Koichi Kato

Affiliation

¹ Department of Structural Biology and Biomolecular Engineering, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.

PMID: 17206147
DOI: 10.1038/nsmb1191

Abstract

Although cullin-1 neddylation is crucial for the activation of SCF ubiquitin E3 ligases, the underlying mechanisms for NEDD8-mediated activation of SCF remain unclear. Here we demonstrate by NMR and mutational studies that NEDD8 binds the ubiquitin E2 (UBC4), but not NEDD8 E2 (UBC12). Our data imply that NEDD8 forms an active platform on the SCF complex for selective recruitment of ubiquitin-charged E2s in collaboration with RBX1, and thereby upregulates the E3 activity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carrier Proteins / chemistry
Cell Cycle Proteins / chemistry*
Cullin Proteins / chemistry*
Humans
Magnetic Resonance Spectroscopy
Models, Molecular
Mutation
NEDD8 Protein
Polyubiquitin / chemistry
Protein Binding
SKP Cullin F-Box Protein Ligases / chemistry*
Ubiquitins / chemistry*
Ubiquitins / genetics
Up-Regulation

Substances

Carrier Proteins
Cell Cycle Proteins
Cullin 1
Cullin Proteins
NEDD8 Protein
NEDD8 protein, human
RBX1 protein, human
Ubiquitins
Polyubiquitin
SKP Cullin F-Box Protein Ligases