Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex.
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 beta-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 A 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.
Mesh Terms:
Amino Acid Motifs, Amino Acid Sequence, Binding Sites, Cell Cycle Proteins, Crystallography, X-Ray, Cullin Proteins, Cyclin-Dependent Kinase Inhibitor p27, Humans, Ligases, Macromolecular Substances, Models, Molecular, Molecular Sequence Data, Peptide Synthases, Protein Binding, Protein Structure, Quaternary, Protein Structure, Tertiary, S-Phase Kinase-Associated Proteins, SKP Cullin F-Box Protein Ligases, Sequence Alignment, Sequence Homology, Amino Acid, Structure-Activity Relationship, Tumor Suppressor Proteins, Ubiquitin, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, Ubiquitins
Amino Acid Motifs, Amino Acid Sequence, Binding Sites, Cell Cycle Proteins, Crystallography, X-Ray, Cullin Proteins, Cyclin-Dependent Kinase Inhibitor p27, Humans, Ligases, Macromolecular Substances, Models, Molecular, Molecular Sequence Data, Peptide Synthases, Protein Binding, Protein Structure, Quaternary, Protein Structure, Tertiary, S-Phase Kinase-Associated Proteins, SKP Cullin F-Box Protein Ligases, Sequence Alignment, Sequence Homology, Amino Acid, Structure-Activity Relationship, Tumor Suppressor Proteins, Ubiquitin, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, Ubiquitins
Nature
Date: Apr. 18, 2002
PubMed ID: 11961546
View in: Pubmed Google Scholar
Download Curated Data For This Publication
11610
Switch View:
- Interactions 3