Suprafacial Orientation of the SCF[superscript Cdc4] Dimer Accommodates Multiple Geometries for Substrate Ubiquitination
- Cellgene
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{sup Cdc4} toward the CDK inhibitor Sic1 and other substrates. SCF{sup Cdc4} dimerization has little effect on the affinity for Sic1 but markedly stimulates ubiquitin conjugation. A model of the dimeric holo-SCF{sup 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 {angstrom} within and 102 {angstrom} 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.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 1007591
- Journal Information:
- Cell, Vol. 129, Issue (6) ; 06, 2007; ISSN 0092-8674
- Country of Publication:
- United States
- Language:
- ENGLISH
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