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Insights into degron recognition by APC/C coactivators from the structure of an Acm1-Cdh1 complex

DOI: 10.1016/j.molcel.2013.04.024 DOI Help
PMID: 23707760 PMID Help

Authors: Jun He (Institute of Cancer Research) , William C. H. Chao (Institute of Cancer Research) , Ziguo Zhang (Institute of Cancer Research) , Jing Yang (Institute of Cancer Research) , Nora Cronin (Institute of Cancer Research) , David Barford (Institute of Cancer Research)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Molecular Cell

State: Published (Approved)
Published: May 2013

Open Access Open Access

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 Keywords: Anaphase-Promoting; Animals; Binding; Cdh1; Cell; Crystallography; X-Ray; Models; Molecular; Protein; Repressor; Saccharomyces; Ubiquitin-Protein Ligase Complexes

Subject Areas: Biology and Bio-materials

Instruments: I04-1-Macromolecular Crystallography (fixed wavelength)

Other Facilities: SWING at SOLEIL

Added On: 05/06/2013 08:41


Discipline Tags:

Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)