Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex Journal Article
| Authors: | Zheng, N.; Schulman, B. A.; Song, L.; Miller, J. J.; Jeffrey, P. D.; Wang, P.; Chu, C.; Koepp, D. M.; Elledge, S. J.; Pagano, M.; Conaway, R. C.; Conaway, J. W.; Harper, J. W.; Pavletich, N. P. |
| Article Title: | Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex |
| Abstract: | SCF complexes are the largest family of E3 ubiquitin-protein ligases and mediate the ubiquitination of diverse regulatory and signalling proteins. Here we present the crystal structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF complex, which shows that Cul1 is an elongated protein that consists of a long stalk and a globular domain. The globular domain binds the RING finger protein Rbx1 through an intermolecular β-sheet, forming a two-subunit catalytic core that recruits the ubiquitin-conjugating enzyme. The long stalk, which consists of three repeats of a novel five-helix motif, binds the Skp1-F boxSkp2 protein substrate-recognition complex at its tip. Cul1 serves as a rigid scaffold that organizes the Skp1-F boxSkp2 and Rbx1 subunits, holding them over 100 Å apart. The structure suggests that Cul1 may contribute to catalysis through the positioning of the substrate and the ubiquitin-conjugating enzyme, and this model is supported by Cul1 mutations designed to eliminate the rigidity of the scaffold. |
| Keywords: | unclassified drug; nonhuman; ubiquitin; cell cycle proteins; complex formation; ubiquitin protein ligase; protein; protein binding; structure-activity relationship; ubiquitination; amino acid sequence; molecular sequence data; sequence homology, amino acid; sequence alignment; protein p27; cyclin-dependent kinase inhibitor p27; tumor suppressor proteins; binding site; crystal structure; hydrogen bond; models, molecular; crystallography, x-ray; protein structure, tertiary; binding sites; molecular interaction; catalysis; crystallization; structure analysis; enzyme structure; ubiquitin-conjugating enzymes; biochemistry; protein structure, quaternary; ubiquitin-protein ligases; mutagenesis; enzymes; substrates; amino acid motifs; s phase kinase associated protein 2; s-phase kinase-associated proteins; skp cullin f-box protein ligases; cullin; cullin proteins; macromolecular substances; ubiquitins; ubiquitin conjugating enzyme; ligases; peptide synthases; f box protein; humans; human; priority journal; article; rbx1 protein; skp1 protein |
| Journal Title: | Nature |
| Volume: | 416 |
| Issue: | 6882 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2002-04-18 |
| Start Page: | 703 |
| End Page: | 709 |
| Language: | English |
| DOI: | 10.1038/416703a |
| PUBMED: | 11961546 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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