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The APC/C subunit Cdc16/Cut9 is a contiguous tetratricopeptide repeat superhelix with a homo‐dimer interface similar to Cdc27
Author(s) -
Zhang Ziguo,
Kulkarni Kiran,
Hanrahan Sarah J,
Thompson Andrew J,
Barford David
Publication year - 2010
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2010.247
Subject(s) - biology , tetratricopeptide , superhelix , protein subunit , dimer , cyclopentane , microbiology and biotechnology , genetics , stereochemistry , gene , physics , dna replication , chemistry , dna supercoil , nuclear magnetic resonance
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.