1T2M

Solution Structure Of The Pdz Domain Of AF-6

1T2M の概要

• エントリーDOI: 10.2210/pdb1t2m/pdb
• 分子名称: AF-6 protein (1 entity in total)
• 機能のキーワード: chromosomal translocation, proto-oncogene, protein binding
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell junction, adherens junction: P55196
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 10637.20

構造登録者

Zhou, H.,Wu, J.H.,Xu, Y.Q.,Huang, A.D.,Shi, Y.Y. (登録日: 2004-04-22, 公開日: 2005-02-08, 最終更新日: 2024-05-29)

主引用文献

Zhou, H.,Xu, Y.,Yang, Y.,Huang, A.,Wu, J.,Shi, Y.
Solution Structure of AF-6 PDZ Domain and Its Interaction with the C-terminal Peptides from Neurexin and Bcr
J.Biol.Chem., 280:13841-13847, 2005

PubMed Abstract: AF-6 is a key molecule essential for structure organization of cell-cell junction of polarized epithelia. It belongs to a novel cell-cell adhesion system. The AF-6 PDZ domain mediates interactions by binding to a specific amino acid sequence in target proteins. Here we report the solution structure of the AF-6 PDZ domain determined by NMR. Previously, the AF-6 PDZ domain was considered to be a class II PDZ domain. However we found that a unique hydrophilic amino acid, Gln70, at position alphaB1 makes the alphaB/betaB groove of the AF-6 PDZ domain significantly different from that of the canonical class II PDZ domain. The AF-6 PDZ domain does not have the second hydrophobic binding pocket, and the N-terminal end of alphaB is closer to betaB. Using BIACORE and NMR chemical shift perturbation experiments, we have studied the binding characteristics of the PDZ domain to the C-terminal peptide of Neurexin, KKNKDKEYYV, and that of Bcr, KRQSILFSTEV. The C-terminal peptide of Neurexin is a class II ligand, whereas that of Bcr is a class I ligand. The dissociation constants of these ligands were 4.08 x 10(-7) and 2.23 x 10(-6) m, respectively. Each of the four C-terminal positions in Neurexin and Bcr may contribute to the interaction. The three-dimensional models of the AF-6 PDZ-Neurexin C-terminal peptide complex and the AF-6 PDZ-Bcr C-terminal peptide complex were built up by molecular dynamics simulations. Unlike the canonical class II PDZ domain, Ala74 at alphaB5 rather than the residue at alphaB1 makes direct hydrophobic contact with the side chain of Tyr at the -2 position of the ligand.

PubMed: 15684424
DOI: 10.1074/jbc.M411065200

実験手法

SOLUTION NMR