Structure of a c-Cbl–UbcH7 Complex
Open accessAbstract
Ubiquitin-protein ligases (E3s) regulate diverse cellular processes by mediating protein ubiquitination. The c-Cbl proto-oncogene is a RING family E3 that recognizes activated receptor tyrosine kinases, promotes their ubiquitination by a ubiquitin-conjugating enzyme (E2) and terminates signaling. The crystal structure of c-Cbl bound to a cognate E2 and a kinase peptide shows how the RING domain recruits the E2. A comparison with a HECT family E3-E2 complex indicates that a common E2 motif is recognized by the two E3 families. The structure reveals a rigid coupling between the peptide binding and the E2 binding domains and a conserved surface channel leading from the peptide to the E2 active site, suggesting that RING E3s may function as scaffolds that position the substrate and the E2 optimally for ubiquitin transfer.
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None of the generated RING mutations, including V389A and V420A, resulted in marked changes in degradation of the LDLR or VLDLR.
“None of the mutations we generated, including V389A and V420A that correspond to the detrimental Ile-383 and Phe-418 in c-Cbl (17), resulted in marked changes in degradation of the LDLR (Fig. 2B) or VLDLR (Fig. 2C).”
From Distinct Functional Domains Contribute to Degradation of the Low Density Lipoprotein Receptor (LDLR) by the E3 Ubiquitin Ligase Inducible Degrader of the LDLR (IDOL) (2011) · cites this paper as [17]
The c-Cbl–UbcH7 interface passage (section labeled Abstract; page unavailable) identifies Ile-383 and Phe-418 as residues that contact UbcH7, supporting the cited comparison of RING residues. Our copy does not show that mutations of those two c-Cbl residues are detrimental. The LDLR and VLDLR degradation results are the citing authors’ own findings, not findings attributed to this source. (LLM, conf=0.82)
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- [1]1. Andoniou, C.E. ∙ Thien, C.B. ∙ Langdon, W.Y. Tumor induction by activated abl involves tyrosine phosphorylation of the product of the cbl oncogene EMBO J. 1994; 13:4515-4523 Crossref Scopus (221) PubMed Google Scholar
- [2]2. Bellon, S.F. ∙ Rodgers, K.K. ∙ Schatz, D.G. ... Crystal structure of the RAG1 dimerization domain reveals multiple zinc-binding motifs including a novel zinc binuclear cluster Nat. Struct. Biol. 1997; 4:586-591 Crossref Scopus (131) PubMed Google Scholar
- [3]3. Blake, T.J. ∙ Shapiro, M. ∙ Morse, H.C. ... The sequences of the human and mouse c-cbl proto-oncogenes show v-cbl was generated by a large truncation encompassing a proline-rich domain and a leucine zipper-like motif Oncogene. 1991; 6:653-657 PubMed Google Scholar
- [6]6. Cook, W.J. ∙ Jeffrey, L.C. ∙ Sullivan, M.L. ... Three-dimensional structure of a ubiquitin-conjugating enzyme (E2) J. Biol. Chem. 1992; 267:15116-15121
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- Authors
- Zheng, N., Wang, P., Jeffrey, P. D., & Pavletich, N. P.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Pavletich, Nikola P.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2000-08
- Volume
- 102
- Issue
- 4
- Pages
- 533-539
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2015291446
- Cited by
- 839
- References
- 0
- Citations by year
- 2026: 12 · 2025: 15 · 2024: 9 · 2023: 13 · 2022: 14 · 2021: 17 · 2020: 16 · 2019: 14 · 2018: 13 · 2017: 24 · 2016: 22 · 2015: 27 · 2014: 20 · 2013: 46 · 2012: 38
- FWCI
- 18.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- 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 Kinase Regulation and GTPase Signaling
- Keywords
- c-Cbl, UbcH7, E3 ubiquitin ligase, RING domain, E2 ubiquitin-conjugating enzyme, ubiquitin-protein ligase, ubiquitination, crystal structure
- MeSH terms
- Proto-Oncogene Mas, Amino Acid Sequence, Animals, Drosophila, Humans, Ligases, Models, Molecular, Molecular Conformation, Molecular Sequence Data, Protein Conformation, Proto-Oncogene Proteins, Structure-Activity Relationship, Caenorhabditis elegans, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, Macromolecular Substances, Proto-Oncogene Proteins c-cbl
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