TY - JOUR
T1 - Substrate binding on the APC/C occurs between the coactivator Cdh1 and the processivity factor Doc1
AU - Buschhorn, Bettina A.
AU - Petzold, Georg
AU - Galova, Marta
AU - Dube, Prakash
AU - Kraft, Claudine
AU - Herzog, Franz
AU - Stark, Holger
AU - Peters, Jan Michael
PY - 2011/1
Y1 - 2011/1
N2 - 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.
AB - 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.
KW - Anaphase-Promoting Complex-Cyclosome
KW - Antigens, CD
KW - Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome
KW - Apc10 Subunit, Anaphase-Promoting Complex-Cyclosome
KW - Apc11 Subunit, Anaphase-Promoting Complex-Cyclosome
KW - Apc2 Subunit, Anaphase-Promoting Complex-Cyclosome
KW - Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome
KW - Apc6 Subunit, Anaphase-Promoting Complex-Cyclosome
KW - Cadherins/metabolism
KW - Cdh1 Proteins
KW - Cell Cycle Proteins/metabolism
KW - Cytokines/metabolism
KW - Humans
KW - Intracellular Signaling Peptides and Proteins
KW - Saccharomyces cerevisiae/enzymology
KW - Saccharomyces cerevisiae Proteins/metabolism
KW - Ubiquitin-Protein Ligase Complexes/chemistry
KW - Ubiquitin-Protein Ligases/metabolism
KW - Ubiquitination
UR - http://www.scopus.com/inward/record.url?scp=78650982520&partnerID=8YFLogxK
U2 - 10.1038/nsmb.1979
DO - 10.1038/nsmb.1979
M3 - Article
C2 - 21186364
AN - SCOPUS:78650982520
SN - 1545-9993
VL - 18
SP - 6
EP - 13
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 1
ER -
