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Suprafacial orientation of the SCFCdc4 dimer accommodates multiple geometries for substrate ubiquitination.

Cell | Jun 15, 2007

SCF ubiquitin ligases recruit substrates for degradation via F box protein adaptor subunits. WD40 repeat F box proteins, such as Cdc4 and beta-TrCP, contain a conserved dimerization motif called the D domain. Here, we report that the D domain protomers of yeast Cdc4 and human beta-TrCP form a superhelical homotypic dimer. Disruption of the D domain compromises the activity of yeast SCF(Cdc4) toward the CDK inhibitor Sic1 and other substrates. SCF(Cdc4) dimerization has little effect on the affinity for Sic1 but markedly stimulates ubiquitin conjugation. A model of the dimeric holo-SCF(Cdc4) complex based on small-angle X-ray scatter measurements reveals a suprafacial configuration, in which substrate-binding sites and E2 catalytic sites lie in the same plane with a separation of 64 A within and 102 A between each SCF monomer. This spatial variability may accommodate diverse acceptor lysine geometries in both substrates and the elongating ubiquitin chain and thereby increase catalytic efficiency.

Pubmed ID: 17574027 RIS Download

Mesh terms: Amino Acid Sequence | Binding Sites | Catalytic Domain | Cell Cycle Proteins | Dimerization | F-Box Proteins | Models, Molecular | Molecular Conformation | Molecular Sequence Data | Protein Binding | Protein Conformation | Protein Structure, Tertiary | SKP Cullin F-Box Protein Ligases | Saccharomyces cerevisiae | Saccharomyces cerevisiae Proteins | Sequence Homology, Amino Acid | Ubiquitin | Ubiquitin-Protein Ligases

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Associated grants

  • Agency: NCRR NIH HHS, Id: RR-08630

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