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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2007-6-18
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pubmed:databankReference |
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0092-8674
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
129
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1165-76
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:17574027-Amino Acid Sequence,
pubmed-meshheading:17574027-Binding Sites,
pubmed-meshheading:17574027-Catalytic Domain,
pubmed-meshheading:17574027-Cell Cycle Proteins,
pubmed-meshheading:17574027-Dimerization,
pubmed-meshheading:17574027-F-Box Proteins,
pubmed-meshheading:17574027-Models, Molecular,
pubmed-meshheading:17574027-Molecular Conformation,
pubmed-meshheading:17574027-Molecular Sequence Data,
pubmed-meshheading:17574027-Protein Binding,
pubmed-meshheading:17574027-Protein Conformation,
pubmed-meshheading:17574027-Protein Structure, Tertiary,
pubmed-meshheading:17574027-SKP Cullin F-Box Protein Ligases,
pubmed-meshheading:17574027-Saccharomyces cerevisiae,
pubmed-meshheading:17574027-Saccharomyces cerevisiae Proteins,
pubmed-meshheading:17574027-Sequence Homology, Amino Acid,
pubmed-meshheading:17574027-Ubiquitin,
pubmed-meshheading:17574027-Ubiquitin-Protein Ligases
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pubmed:year |
2007
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pubmed:articleTitle |
Suprafacial orientation of the SCFCdc4 dimer accommodates multiple geometries for substrate ubiquitination.
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pubmed:affiliation |
Centre for Systems Biology, Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada M5G 1X5.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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