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Molecular Structure of the N-terminal Domain of the APC/C Subunit Cdc27 Reveals a Homo-dimeric Tetratricopeptide Repeat Architecture

DOI: 10.1016/j.jmb.2010.02.045 DOI Help
PMID: 20206185 PMID Help

Authors: Ziguo Zhang (Institute of Cancer Research) , Mark Roe (Institute of Cancer Research,) , Marie Diogon (Génome et Environnement) , Eric Kong (Institute of Cancer Research) , Hicham El Alaoui (Génome et Environnement) , David Barford (Institute of Cancer Research)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Molecular Biology , VOL 397 (5) , PAGES 1316-1328

State: Published (Approved)
Published: April 2010

Abstract: The anaphase promoting complex/cyclosome (APC/C) is a large multi-subunit E3 ubiquitin ligase that targets specific cell cycle regulatory proteins for ubiquitin-dependent degradation, thereby controlling cell cycle events such as the metaphase to anaphase transition and the exit from mitosis. Biochemical and genetic studies are consistent with the notion that subunits of APC/C are organised into two distinct sub-complexes; a catalytic sub-complex including the cullin domain and RING finger subunits Apc2 and Apc11, respectively, and a tetratricopeptide repeat (TPR) sub-complex composed of the TPR subunits Cdc16, Cdc23 and Cdc27 (Apc3). Here, we describe the crystal structure of the N-terminal domain of Encephalitozoon cuniculi Cdc27 (Cdc27Nterm), revealing a homo-dimeric structure, composed predominantly of successive TPR motifs. Mutation of the Cdc27Nterm dimer interface destabilises the protein, disrupts dimerisation in solution, and abolishes the capacity of E. cuniculi Cdc27 to complement Saccharomyces cerevisiae Cdc27 in vivo. These results establish the existence of functional APC/C genes in E. cuniculi, the evolutionarily conserved dimeric properties of Cdc27, and provide a framework for understanding the architecture of full-length Cdc27.

Journal Keywords: Apc2; Anaphase-Promoting; Apc3; Anaphase-Promoting; Apc8; Anaphase-Promoting; Crystallography; X-Ray; Encephalitozoon; Molecular; Protein; Tertiary; Repetitive; Amino; Saccharomyces; Ubiquitin-Protein; Ubiquitin-Protein Ligases

Subject Areas: Biology and Bio-materials


Instruments: I02-Macromolecular Crystallography

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