Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex

Nature. 2002 Apr 18;416(6882):703-9. doi: 10.1038/416703a.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Binding Sites
  • Cell Cycle Proteins / chemistry*
  • Cell Cycle Proteins / metabolism
  • Crystallography, X-Ray
  • Cullin Proteins*
  • Cyclin-Dependent Kinase Inhibitor p27
  • Humans
  • Ligases / chemistry*
  • Ligases / metabolism
  • Macromolecular Substances
  • Models, Molecular
  • Molecular Sequence Data
  • NEDD8 Protein
  • Peptide Synthases / chemistry*
  • Peptide Synthases / metabolism
  • 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 / metabolism
  • Ubiquitin / metabolism
  • Ubiquitin-Conjugating Enzymes
  • Ubiquitin-Protein Ligases
  • Ubiquitins / metabolism

Substances

  • Cell Cycle Proteins
  • Cullin 1
  • Cullin Proteins
  • Macromolecular Substances
  • NEDD8 Protein
  • NEDD8 protein, human
  • S-Phase Kinase-Associated Proteins
  • Tumor Suppressor Proteins
  • Ubiquitin
  • Ubiquitins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Ubiquitin-Conjugating Enzymes
  • SKP Cullin F-Box Protein Ligases
  • Ubiquitin-Protein Ligases
  • Ligases
  • Peptide Synthases

Associated data

  • PDB/1LDD
  • PDB/1LDJ
  • PDB/1LDK