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The APC/C subunit Cdc16/Cut9 is a contiguous tetratricopeptide repeat superhelix with a homo-dimer interface similar to Cdc27

DOI: 10.1038/emboj.2010.247 DOI Help
PMID: 20924356 PMID Help

Authors: Ziguo Zhang (Institute of Cancer Research) , Kiran Kulkarni (Institute of Cancer Research) , Sarah Hanrahan (Institute of Cancer Research) , Andrew J. Thompson (Institute of Cancer Research) , David Barford (Institute of Cancer Research)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: The Embo Journal

State: Published (Approved)
Published: September 2010

Abstract: The anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase responsible for controlling cell cycle transitions, is a multisubunit complex assembled from 13 different proteins. Numerous APC/C subunits incorporate multiple copies of the tetratricopeptide repeat (TPR). Here, we report the crystal structure of Schizosaccharomyces pombe Cut9 (Cdc16/Apc6) in complex with Hcn1 (Cdc26), showing that Cdc16/Cut9 is a contiguous TPR superhelix of 14 TPR units. A C-terminal block of TPR motifs interacts with Hcn1, whereas an N-terminal TPR block mediates Cdc16/Cut9 self-association through a homotypic interface. This dimer interface is structurally related to the N-terminal dimerization domain of Cdc27, demonstrating that both Cdc16/Cut9 and Cdc27 form homo-dimers through a conserved mechanism. The acetylated N-terminal Met residue of Hcn1 is enclosed within a chamber created from the Cut9 TPR superhelix. Thus, in complex with Cdc16/Cut9, the N-acetyl-Met residue of Hcn1, a putative degron for the Doa10 E3 ubiquitin ligase, is inaccessible for Doa10 recognition, protecting Hcn1/Cdc26 from ubiquitin-dependent degradation. This finding may provide a structural explanation for a mechanism to control the stoichiometry of proteins participating in multisubunit complexes.

Journal Keywords: Anaphase-Promoting; Apc6; Anaphase-Promoting; Crystallization; Crystallography; X-Ray; DNA; Evolution; Molecular; Nuclear; Protein; Repetitive; Amino; Repressor; Schizosaccharomyces; Schizosaccharomyces; Sequence; Amino; Spectrometry; Mass; Matrix-Assisted Laser Desorption-Ionization

Subject Areas: Biology and Bio-materials

Instruments: I02-Macromolecular Crystallography

Added On: 12/10/2010 14:06

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