Crystal structures of the armadillo repeat domain of adenomatous polyposis coli and its complex with the tyrosine-rich domain of Sam68

Ella Czarina Morishita; Kazutaka Murayama; Miyuki Kato-Murayama; Yoshiko Ishizuka-Katsura; Yuri Tomabechi; Tomoatsu Hayashi; Takaho Terada; Noriko Handa; Mikako Shirouzu; Tetsu Akiyama; Shigeyuki Yokoyama

doi:10.1016/j.str.2011.07.013

Crystal structures of the armadillo repeat domain of adenomatous polyposis coli and its complex with the tyrosine-rich domain of Sam68

Structure. 2011 Oct 12;19(10):1496-508. doi: 10.1016/j.str.2011.07.013.

Authors

Ella Czarina Morishita¹, Kazutaka Murayama, Miyuki Kato-Murayama, Yoshiko Ishizuka-Katsura, Yuri Tomabechi, Tomoatsu Hayashi, Takaho Terada, Noriko Handa, Mikako Shirouzu, Tetsu Akiyama, Shigeyuki Yokoyama

Affiliation

¹ RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045, Japan.

PMID: 22000517
DOI: 10.1016/j.str.2011.07.013

Abstract

Adenomatous polyposis coli (APC) is a tumor suppressor protein commonly mutated in colorectal tumors. APC plays important roles in Wnt signaling and other cellular processes. Here, we present the crystal structure of the armadillo repeat (Arm) domain of APC, which facilitates the binding of APC to various proteins. APC-Arm forms a superhelix with a positively charged groove. We also determined the structure of the complex of APC-Arm with the tyrosine-rich (YY) domain of the Src-associated in mitosis, 68 kDa protein (Sam68), which regulates TCF-1 alternative splicing. Sam68-YY forms numerous interactions with the residues on the groove and is thereby fixed in a bent conformation. We assessed the effects of mutations and phosphorylation on complex formation between APC-Arm and Sam68-YY. Structural comparisons revealed different modes of ligand recognition between the Arm domains of APC and other Arm-containing proteins.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / chemistry*
Adenomatous Polyposis Coli Protein / chemistry*
Alternative Splicing
Cloning, Molecular
Computer Simulation
DNA-Binding Proteins / chemistry*
Escherichia coli / genetics
Escherichia coli / metabolism
Humans
Multiprotein Complexes / chemistry*
Mutation, Missense
Phosphorylation
Protein Binding
Protein Interaction Mapping
Protein Structure, Secondary
RNA-Binding Proteins / chemistry*
Selenomethionine / chemistry
X-Ray Diffraction

Substances

APC protein, human
Adaptor Proteins, Signal Transducing
Adenomatous Polyposis Coli Protein
DNA-Binding Proteins
KHDRBS1 protein, human
Multiprotein Complexes
RNA-Binding Proteins
Selenomethionine

Associated data

PDB/3AU3
PDB/3QHE