3DJ3

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

Summary for 3DJ3

• Entry DOI: 10.2210/pdb3dj3/pdb
• Related: 3DIW 3DJ1
• Descriptor: Tax1-binding protein 3 (2 entities in total)
• Functional Keywords: tip-1, pdz domain, cytoplasm, nucleus, wnt signaling pathway, signaling protein
• Biological source: Mus musculus (mouse)
• Cellular location: Cytoplasm: Q9DBG9
• Total number of polymer chains: 4
• Total formula weight: 50032.76

Authors

Shen, Y. (deposition date: 2008-06-21, release date: 2008-10-21, Last modification date: 2023-11-01)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.4 Å)