Abstract:
:The anaphase-promoting complex/cyclosome (APC/C) regulates sister chromatid segregation and the exit from mitosis. Selection of most APC/C substrates is controlled by coactivator subunits (either Cdc20 or Cdh1) that interact with substrate destruction motifs--predominantly the destruction (D) box and KEN box degrons. How coactivators recognize D box degrons and how this is inhibited by APC/C regulatory proteins is not defined at the atomic level. Here, from the crystal structure of S. cerevisiae Cdh1 in complex with its specific inhibitor Acm1, which incorporates D and KEN box pseudosubstrate motifs, we describe the molecular basis for D box recognition. Additional interactions between Acm1 and Cdh1 identify a third protein-binding site on Cdh1 that is likely to confer coactivator-specific protein functions including substrate association. We provide a structural rationalization for D box and KEN box recognition by coactivators and demonstrate that many noncanonical APC/C degrons bind APC/C coactivators at the D box coreceptor.
journal_name
Mol Celljournal_title
Molecular cellauthors
He J,Chao WC,Zhang Z,Yang J,Cronin N,Barford Ddoi
10.1016/j.molcel.2013.04.024subject
Has Abstractpub_date
2013-06-06 00:00:00pages
649-60issue
5eissn
1097-2765issn
1097-4164pii
S1097-2765(13)00329-8journal_volume
50pub_type
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