title: Crystal structures of the armadillo repeat domain of adenomatous polyposis coli and its complex with the tyrosine-rich domain of Sam68.
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.
authors: RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045, Japan.
authors: Ella Czarina
authors: EC
authors: Morishita
authors: Kazutaka
authors: K
authors: Murayama
authors: Miyuki
authors: M
authors: Kato-Murayama
authors: Yoshiko
authors: Y
authors: Ishizuka-Katsura
authors: Yuri
authors: Y
authors: Tomabechi
authors: Tomoatsu
authors: T
authors: Hayashi
authors: Takaho
authors: T
authors: Terada
authors: Noriko
authors: N
authors: Handa
authors: Mikako
authors: M
authors: Shirouzu
authors: Tetsu
authors: T
authors: Akiyama
authors: Shigeyuki
authors: S
authors: Yokoyama
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry*; D025601:Adenomatous Polyposis Coli Protein / Q000737:chemistry*; D017398:Alternative Splicing; D003001:Cloning, Molecular; D003198:Computer Simulation; D004268:DNA-Binding Proteins / Q000737:chemistry*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006801:Humans; D046912:Multiprotein Complexes / Q000737:chemistry*; D020125:Mutation, Missense; D010766:Phosphorylation; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017433:Protein Structure, Secondary; D016601:RNA-Binding Proteins / Q000737:chemistry*; D012645:Selenomethionine / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: C555337:APC protein, human; D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein; D004268:DNA-Binding Proteins; C489559:KHDRBS1 protein, human; D046912:Multiprotein Complexes; D016601:RNA-Binding Proteins; D012645:Selenomethionine