2XPI: Crystal Structure Of ApcC HETERO-Tetramer Cut9-Hcn1

Citation:
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.
PDB ID: 2XPIDownload
MMDB ID: 89475
PDB Deposition Date: 2010/8/26
Updated in MMDB: 2012/12
Experimental Method:
x-ray diffraction
Resolution: 2.6  Å
Source Organism:
Similar Structures:
Biological Unit for 2XPI: tetrameric; determined by author and by software (PISA)
Molecular Components in 2XPI
Label Count Molecule
Proteins (4 molecules)
2
Anaphase-promoting Complex Subunit Cut9(Gene symbol: cut9)
Molecule annotation
2
Anaphase-promoting Complex Subunit Hcn1 Hcn1/cdc26,20s Cyclosome/apc Complex Protein Hcn1, Chaperone-like Protein Hcn1, High Copy Suppressor of Cut9 Protein 1(Gene symbol: hcn1)
Molecule annotation
Chemicals (4 molecules)
1
4
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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