3DJ3

Crystal Structure of C-terminal Truncated TIP-1 (6-113)

3DJ3 の概要

• エントリーDOI: 10.2210/pdb3dj3/pdb
• 関連するPDBエントリー: 3DIW 3DJ1
• 分子名称: Tax1-binding protein 3 (2 entities in total)
• 機能のキーワード: tip-1, pdz domain, cytoplasm, nucleus, wnt signaling pathway, signaling protein
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Cytoplasm: Q9DBG9
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 50032.76

構造登録者

Shen, Y. (登録日: 2008-06-21, 公開日: 2008-10-21, 最終更新日: 2023-11-01)

主引用文献

Zhang, J.,Yan, X.,Shi, C.,Yang, X.,Guo, Y.,Tian, C.,Long, J.,Shen, Y.
Structural Basis of beta-Catenin Recognition by Tax-interacting Protein-1
J.Mol.Biol., 384:255-263, 2008

PubMed Abstract: Tax-interacting protein-1 (TIP-1) is an unusual signaling protein, containing a single PDZ domain. TIP-1 is able to bind beta-catenin with high affinity and thus inhibit its transcriptional activity. The high-resolution crystal structure of TIP-1 in complex with the C-terminal peptide of beta-catenin provides molecular details for the recognition of beta-catenin by TIP-1. Moreover, structural comparison of peptide-free and peptide-bound TIP-1 reveals that significant conformational changes are required in the betaB-betaC loop region of TIP-1 to avoid clashes with the incoming C-terminal beta-catenin peptide. Such conformational changes have not been observed in other structures of PDZ domains. In addition to the canonical peptide-binding pocket of the PDZ domain, TIP-1 can form a binding cavity to anchor more amino acids through a conserved hydrophobic residue pair (Trp776 of beta-catenin and Pro45 of TIP-1). Structural and biochemical data indicate that the canonical binding pocket together with the hydrophobic residue pair are presumably the major cause of the significantly higher affinity of the beta-catenin C-terminal to TIP-1 than to other PDZ domains, providing a unique binding specificity. Our results reveal the molecular mechanism of TIP-1 as an antagonist in PDZ domain signaling.

PubMed: 18835279
DOI: 10.1016/j.jmb.2008.09.034

実験手法

X-RAY DIFFRACTION (2.4 Å)