TY - JOUR
T1 - Crystal structures of the armadillo repeat domain of adenomatous polyposis coli and its complex with the tyrosine-rich domain of Sam68
AU - Morishita, Ella Czarina
AU - Murayama, Kazutaka
AU - Kato-Murayama, Miyuki
AU - Ishizuka-Katsura, Yoshiko
AU - Tomabechi, Yuri
AU - Hayashi, Tomoatsu
AU - Terada, Takaho
AU - Handa, Noriko
AU - Shirouzu, Mikako
AU - Akiyama, Tetsu
AU - Yokoyama, Shigeyuki
N1 - Funding Information:
We thank R. Akasaka, M. Aoki, K. Honda, M. Inoue, T. Itagaki, K. Katsura, N. Maoka, N. Ohsawa, H. Shimizu, N. Shinya, M. Toyama, and T. Uchikubo-Kamo for help with sample preparation; T. Hosaka for X-ray diffraction data collection; T. Kasai and N. Tochio for technical assistance during ITC measurements; L.J. Parker for advice on data processing and structure determination, and for critical reading of the manuscript; and A. Shimada for assistance during ITC measurements and for helpful discussions. We thank the Support Unit for Bio-material Analysis, RIKEN BSI Research Resources Center, especially A. Abe, J. Ishikawa, and R. Ito, for synthesis of the Sam68 peptides; and the SPring-8 and SLS staffs for support. This work was supported by the RIKEN Structural Genomics/Proteomics Initiative (RSGI), the National Project on Protein Structural and Functional Analyses, and the Targeted Proteins Research Program (TPRP) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan.
PY - 2011/10/12
Y1 - 2011/10/12
N2 - 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.
AB - 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.
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U2 - 10.1016/j.str.2011.07.013
DO - 10.1016/j.str.2011.07.013
M3 - Article
C2 - 22000517
AN - SCOPUS:80054060426
VL - 19
SP - 1496
EP - 1508
JO - Structure with Folding & design
JF - Structure with Folding & design
SN - 0969-2126
IS - 10
ER -