Structure of the Cul1–Rbx1–Skp1–F boxSkp2 SCF ubiquitin ligase complex
Copyright policy )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.
- Baylor College of Medicine United States
- St. Jude Children's Research Hospital United States
- Howard Hughes Medical Institute United States
- Memorial Sloan Kettering Cancer Center United States
- Stowers Institute for Medical Research United States
Models, Molecular, Binding Sites, SKP Cullin F-Box Protein Ligases, NEDD8 Protein, Macromolecular Substances, Amino Acid Motifs, Molecular Sequence Data, Cell Cycle Proteins, Crystallography, X-Ray, Cullin Proteins, Protein Structure, Tertiary, Ligases, Humans, Amino Acid Sequence, Peptide Synthases, Protein Structure, Quaternary, S-Phase Kinase-Associated Proteins, Sequence Alignment, Cyclin-Dependent Kinase Inhibitor p27, Protein Binding
Models, Molecular, Binding Sites, SKP Cullin F-Box Protein Ligases, NEDD8 Protein, Macromolecular Substances, Amino Acid Motifs, Molecular Sequence Data, Cell Cycle Proteins, Crystallography, X-Ray, Cullin Proteins, Protein Structure, Tertiary, Ligases, Humans, Amino Acid Sequence, Peptide Synthases, Protein Structure, Quaternary, S-Phase Kinase-Associated Proteins, Sequence Alignment, Cyclin-Dependent Kinase Inhibitor p27, Protein Binding
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).1K popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 0.1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 0.1% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 0.1%
Citations provided by BIP!Popularity provided by BIP!