2H2B

Crystal Structure of ZO-1 PDZ1 Bound to a Phage-Derived Ligand (WRRTTYL)

Summary for 2H2B

• Entry DOI: 10.2210/pdb2h2b/pdb
• Related: 2H2C 2H3L 2H3M
• Descriptor: Tight junction protein ZO-1, ACETIC ACID (3 entities in total)
• Functional Keywords: pdz domain, phage derived high affinity ligand, cell adhesion
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Peripheral membrane protein; Cytoplasmic side: Q07157
• Total number of polymer chains: 1
• Total formula weight: 11776.29

Authors

Appleton, B.A.,Zhang, Y.,Wu, P.,Yin, J.P.,Hunziker, W.,Skelton, N.J.,Sidhu, S.S.,Wiesmann, C. (deposition date: 2006-05-18, release date: 2006-06-13, Last modification date: 2023-08-30)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.6 Å)