2H3M

Crystal Structure of ZO-1 PDZ1

2H3M の概要

• エントリーDOI: 10.2210/pdb2h3m/pdb
• 関連するPDBエントリー: 2H2B 2H2C 2H3L
• 分子名称: Tight junction protein ZO-1, SULFATE ION (2 entities in total)
• 機能のキーワード: pdz domain, cell adhesion
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane; Peripheral membrane protein; Cytoplasmic side: Q07157
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 10758.07

構造登録者

Appleton, B.A.,Zhang, Y.,Wu, P.,Yin, J.P.,Hunziker, W.,Skelton, N.J.,Sidhu, S.S.,Wiesmann, C. (登録日: 2006-05-22, 公開日: 2006-06-13, 最終更新日: 2023-08-30)

主引用文献

Appleton, B.A.,Zhang, Y.,Wu, P.,Yin, J.P.,Hunziker, W.,Skelton, N.J.,Sidhu, S.S.,Wiesmann, C.
Comparative structural analysis of the Erbin PDZ domain and the first PDZ domain of ZO-1. Insights into determinants of PDZ domain specificity.
J.Biol.Chem., 281:22312-22320, 2006

PubMed Abstract: We report a structural comparison of the first PDZ domain of ZO-1 (ZO1-PDZ1) and the PDZ domain of Erbin (Erbin-PDZ). Although the binding profile of Erbin-PDZ is extremely specific ([D/E][T/S]WV(COOH)), that of ZO1-PDZ1 is similar ([R/K/S/T][T/S][W/Y][V/I/L](COOH)) but broadened by increased promiscuity for three of the last four ligand residues. Consequently, the biological function of ZO-1 is also broadened, as it interacts with both tight and adherens junction proteins, whereas Erbin is restricted to adherens junctions. Structural analyses reveal that the differences in specificity can be accounted for by two key differences in primary sequence. A reduction in the size of the hydrophobic residue at the base of the site(0) pocket enables ZO1-PDZ1 to accommodate larger C-terminal residues. A single additional difference alters the specificity of both site(-1) and site(-3). In ZO1-PDZ1, an Asp residue makes favorable interactions with both Tyr(-1) and Lys/Arg(-3). In contrast, Erbin-PDZ contains an Arg at the equivalent position, and this side chain cannot accommodate either Tyr(-1) or Lys/Arg(-3) but, instead, interacts favorably with Glu/Asp(-3). We propose a model for ligand recognition that accounts for interactions extending across the entire binding site but that highlights several key specificity switches within the PDZ domain fold.

PubMed: 16737969
DOI: 10.1074/jbc.M602901200

実験手法

X-RAY DIFFRACTION (2.9 Å)