2P64

D domain of b-TrCP

Summary for 2P64

• Entry DOI: 10.2210/pdb2p64/pdb
• Descriptor: F-box/WD repeat protein 1A, CADMIUM ION (3 entities in total)
• Functional Keywords: right handed super-helical bundle, ligase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q9Y297
• Total number of polymer chains: 2
• Total formula weight: 12755.96

Authors

Neculai, D.,Orlicky, S.,Ceccarelli, D. (deposition date: 2007-03-16, release date: 2007-06-19, Last modification date: 2024-10-30)

Primary citation

Tang, X.,Orlicky, S.,Lin, Z.,Willems, A.,Neculai, D.,Ceccarelli, D.,Mercurio, F.,Shilton, B.H.,Sicheri, F.,Tyers, M.
Suprafacial orientation of the SCFCdc4 dimer accommodates multiple geometries for substrate ubiquitination.
Cell(Cambridge,Mass.), 129:1165-1176, 2007

PubMed Abstract: 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: 17574027
DOI: 10.1016/j.cell.2007.04.042

Experimental method

X-RAY DIFFRACTION (2.5 Å)