Structure of a β-TrCP1-Skp1-β-Catenin Complex
Open accessAbstract
The SCF ubiquitin ligases catalyze protein ubiquitination in diverse cellular processes. SCFs bind substrates through the interchangeable F box protein subunit, with the >70 human F box proteins allowing the recognition of a wide range of substrates. The F box protein beta-TrCP1 recognizes the doubly phosphorylated DpSGphiXpS destruction motif, present in beta-catenin and IkappaB, and directs the SCF(beta-TrCP1) to ubiquitinate these proteins at specific lysines. The 3.0 A structure of a beta-TrCP1-Skp1-beta-catenin complex reveals the basis of substrate recognition by the beta-TrCP1 WD40 domain. The structure, together with the previous SCF(Skp2) structure, leads to the model of SCF catalyzing ubiquitination by increasing the effective concentration of the substrate lysine at the E2 active site. The model's prediction that the lysine-destruction motif spacing is a determinant of ubiquitination efficiency is confirmed by measuring ubiquitination rates of mutant beta-catenin peptides, solidifying the model and also providing a mechanistic basis for lysine selection.
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- Authors
- Wu, G., Xu, G., Schulman, B. A., Jeffrey, P. D., Harper, J. W., & Pavletich, N. P.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Pavletich, Nikola P.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2003-06
- Volume
- 11
- Issue
- 6
- Pages
- 1445-1456
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2147291971
- Cited by
- 612
- References
- 41
- Citations by year
- 2026: 19 · 2025: 26 · 2024: 13 · 2023: 18 · 2022: 14 · 2021: 24 · 2020: 30 · 2019: 19 · 2018: 19 · 2017: 20 · 2016: 16 · 2015: 21 · 2014: 37 · 2013: 39 · 2012: 25
- FWCI
- 13.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG011085)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- β-TrCP1, Skp1, β-catenin, SCF ubiquitin ligase, F-box protein, WD40 domain, substrate recognition, ubiquitination, IκB
- MeSH terms
- Amino Acid Sequence, Binding Sites, Cytoskeletal Proteins, Humans, Kinetics, Ligases, Lysine, Models, Molecular, Molecular Sequence Data, Peptides, Protein Binding, Protein Conformation, Substrate Specificity, Trans-Activators, Consensus Sequence, Conserved Sequence, Crystallography, X-Ray, Cell Cycle Proteins, GTP-Binding Proteins, Amino Acid Motifs, Ubiquitin, S-Phase Kinase-Associated Proteins, beta-Transducin Repeat-Containing Proteins, beta Catenin
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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