Substrate binding on the APC/C occurs between the coactivator Cdh1 and the processivity factor Doc1

Nat Struct Mol Biol. 2011 Jan;18(1):6-13. doi: 10.1038/nsmb.1979. Epub 2010 Dec 26.

Abstract

The anaphase-promoting complex/cyclosome (APC/C) is a 22S ubiquitin ligase complex that initiates chromosome segregation and mitotic exit. We have used biochemical and electron microscopic analyses of Saccharomyces cerevisiae and human APC/C to address how the APC/C subunit Doc1 contributes to recruitment and processive ubiquitylation of APC/C substrates, and to understand how APC/C monomers interact to form a 36S dimeric form. We show that Doc1 interacts with Cdc27, Cdc16 and Apc1 and is located in the vicinity of the cullin-RING module Apc2-Apc11 in the inner cavity of the APC/C. Substrate proteins also bind in the inner cavity, in close proximity to Doc1 and the coactivator Cdh1, and induce conformational changes in Apc2-Apc11. Our results suggest that substrates are recruited to the APC/C by binding to a bipartite substrate receptor composed of a coactivator protein and Doc1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome
  • Antigens, CD
  • Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome
  • Apc10 Subunit, Anaphase-Promoting Complex-Cyclosome
  • Apc11 Subunit, Anaphase-Promoting Complex-Cyclosome
  • Apc2 Subunit, Anaphase-Promoting Complex-Cyclosome
  • Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome
  • Apc6 Subunit, Anaphase-Promoting Complex-Cyclosome
  • Cadherins / metabolism*
  • Cdh1 Proteins
  • Cell Cycle Proteins / metabolism*
  • Cytokines / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Ubiquitin-Protein Ligase Complexes / chemistry
  • Ubiquitin-Protein Ligase Complexes / metabolism*
  • Ubiquitin-Protein Ligase Complexes / ultrastructure
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination

Substances

  • ANAPC1 protein, human
  • Antigens, CD
  • Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome
  • Apc10 Subunit, Anaphase-Promoting Complex-Cyclosome
  • Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome
  • Apc6 Subunit, Anaphase-Promoting Complex-Cyclosome
  • CDC16 protein, S cerevisiae
  • CDC27 protein, S cerevisiae
  • CDH1 protein, S cerevisiae
  • CDH1 protein, human
  • Cadherins
  • Cdh1 Proteins
  • Cell Cycle Proteins
  • Cytokines
  • DOC1 protein, S cerevisiae
  • FILIP1L protein, human
  • Intracellular Signaling Peptides and Proteins
  • Saccharomyces cerevisiae Proteins
  • Ubiquitin-Protein Ligase Complexes
  • ANAPC11 protein, human
  • APC2 protein, S cerevisiae
  • Anaphase-Promoting Complex-Cyclosome
  • Apc11 Subunit, Anaphase-Promoting Complex-Cyclosome
  • Apc2 Subunit, Anaphase-Promoting Complex-Cyclosome
  • Ubiquitin-Protein Ligases