Dissertation/Thesis Abstract

Substrate binding by the anaphase-promoting complex
by Matyskiela, Mary E., Ph.D., University of California, San Francisco, 2009, 123; 3378672
Abstract (Summary)

The anaphase-promoting complex or cyclosome (APC/C) is a ubiquitin ligase essential for the completion of mitosis in all eukaryotic cells. Substrates are recruited to the APC/C by activator proteins (Cdc20 or Cdh1), but it is not known where substrates are bound during catalysis. We explored this problem by analyzing mutations in the tetratricopeptide repeat (TPR)-containing APC/C subunits. We identified residues in Cdc23 and Cdc27 that are required for APC/C binding to Cdc20 and Cdh1 and for APC/C function in vivo. Mutation of these sites increased the rate of activator dissociation from the APC/C but did not affect reaction processivity, suggesting that the mutations have little effect on substrate dissociation from the active site. Further studies revealed that activator dissociation from the APC/C is inhibited by substrate, and that substrates are not bound solely to activator during catalysis but interact bivalently with an additional binding site on the APC/C core.

Indexing (document details)
Advisor: Morgan, David O.
Commitee: Narlikar, Geeta J., Weissman, Jonathan S.
School: University of California, San Francisco
Department: Biochemistry and Molecular Biology
School Location: United States -- California
Source: DAI-B 70/10, Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Molecular biology, Biochemistry
Keywords: Anaphase-promoting complex, Substrate binding, Tetratricopeptide repeats, Ubiquitination
Publication Number: 3378672
ISBN: 9781109421507
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