Cited by 280Ubiquitin and proteasome pathwaysEnzyme Structure and FunctionProtein Degradation and Inhibitors

Structure of the Cand1-Cul1-Roc1 Complex Reveals Regulatory Mechanisms for the Assembly of the Multisubunit Cullin-Dependent Ubiquitin Ligases

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Goldenberg, Seth J., Cascio, Thomas C., Shumway, Stuart D., Garbutt, Kenneth C., Liu, Jidong, Xiong, Yue, Zheng, Ning·2004·Cell

Abstract

The SCF ubiquitin ligase complex regulates diverse cellular functions by ubiquitinating numerous protein substrates. Cand1, a 120 kDa HEAT repeat protein, forms a tight complex with the Cul1-Roc1 SCF catalytic core, inhibiting the assembly of the multisubunit E3 complex. The crystal structure of the Cand1-Cul1-Roc1 complex shows that Cand1 adopts a highly sinuous superhelical structure, clamping around the elongated SCF scaffold protein Cul1. At one end, a Cand1 beta hairpin protrusion partially occupies the adaptor binding site on Cul1, inhibiting its interactions with the Skp1 adaptor and the substrate-recruiting F box protein subunits. At the other end, two Cand1 HEAT repeats pack against a conserved Cul1 surface cleft and bury a Cul1 lysine residue, whose modification by the ubiquitin-like protein, Nedd8, is able to block Cand1-Cul1 association. Together with biochemical evidence, these structural results elucidate the mechanisms by which Cand1 and Nedd8 regulate the assembly-disassembly cycles of SCF and other cullin-dependent E3 complexes.

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Crossref · 10.1016/j.cell.2004.10.019

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Authors
Goldenberg, S. J., Cascio, T. C., Shumway, S. D., Garbutt, K. C., Liu, J., Xiong, Y., & Zheng, N.
Affiliations
  • University of Washington (US)
  • University of North Carolina at Chapel Hill (US)
Corresponding author
Zheng, Ning
Venue
Cell
Publisher
Elsevier BV
Published
2004-11
Volume
119
Issue
4
Pages
517-528
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2094021381
Cited by
280
References
85
Citations by year
2026: 2 · 2025: 7 · 2024: 5 · 2023: 14 · 2022: 7 · 2021: 8 · 2020: 14 · 2019: 11 · 2018: 5 · 2017: 14 · 2016: 16 · 2015: 8 · 2014: 11 · 2013: 27 · 2012: 19
FWCI
4.62
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • UNC Libraries
Funders
  • National Cancer Institute (R01CA107134, CA 107134)
  • National Institute of General Medical Sciences (2 T32 GM07270-29, T32GM007270)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
Keywords
SCF ubiquitin ligase, CAND1, CUL1, ROC1, HEAT repeats, NEDD8, F-box protein, crystal structure, protein complex formation, ubiquitination
MeSH terms
Carrier Proteins, Crystallization, Humans, Models, Molecular, Molecular Conformation, Protein Binding, Transcription Factors, Cell Cycle Proteins, Ubiquitin, Ubiquitin-Protein Ligase Complexes, Cullin Proteins, SKP Cullin F-Box Protein Ligases, Adaptor Proteins, Signal Transducing

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