Structure of the Cand1-Cul1-Roc1 Complex Reveals Regulatory Mechanisms for the Assembly of the Multisubunit Cullin-Dependent Ubiquitin Ligases
Open accessAbstract
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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- 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
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3180 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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