Structure of the VHL-elonginC-elonginB complex: Implications for VHL tumor suppressor function Journal Article
| Authors: | Stebbins, C. E.; Kaelin Jr, W. G.; Pavletich, N. P. |
| Article Title: | Structure of the VHL-elonginC-elonginB complex: Implications for VHL tumor suppressor function |
| Abstract: | Mutation of the VHL tumor suppressor is associated with the inherited yon Hippel-Lindau (VHL) cancer syndrome and the majority of kidney cancers. VHL binds the ElonginC-ElonginB complex and regulates levels of hypoxia- inducible proteins. The structure of the ternary complex at 2.7 angstrom resolution shows two interfaces, one between VHL and ElonginC and another between ElonginC and ElonginB. Tumorigenic mutations frequently occur in a 35-residue domain of VHL responsible for ElonginC binding. A mutational patch on a separate domain of VHL indicates a second macromolecular binding site. The structure extends the similarities to the SCF (Skp1-Cul1-F-box protein) complex that targets proteins for degradation, supporting the hypothesis that VHL may function in an analogous pathway. |
| Keywords: | gene mutation; mutation; mutation, missense; disease classification; protein conformation; protein domain; neoplasms; proteins; cell cycle proteins; complex formation; protein degradation; carcinogenesis; transcription factors; cloning, molecular; tumor suppressor gene; amino acid sequence; molecular sequence data; tumor suppressor proteins; binding site; gene control; hydrogen bonding; models, molecular; crystallography, x-ray; binding sites; molecular interaction; protein folding; kidney cancer; molecular biology; von hippel lindau disease; protein structure; structure analysis; ubiquitin-protein ligases; protein structure, secondary; genes, tumor suppressor; s-phase kinase-associated proteins; ligases; crystallography; surface properties; hippel-lindau disease; von hippel-lindau tumor suppressor protein; humans; human; priority journal; article |
| Journal Title: | Science |
| Volume: | 284 |
| Issue: | 5413 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 1999-04-16 |
| Start Page: | 455 |
| End Page: | 461 |
| Language: | English |
| DOI: | 10.1126/science.284.5413.455 |
| PUBMED: | 10205047 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
