3TSZ

crystal structure of PDZ3-SH3-GUK core module from human ZO-1 in complex with 12mer peptide from human JAM-A cytoplasmic tail

Summary for 3TSZ

• Entry DOI: 10.2210/pdb3tsz/pdb
• Related: 3TSV 3TSW
• Descriptor: Tight junction protein ZO-1, Junctional adhesion molecule A (3 entities in total)
• Functional Keywords: pdz3-sh3-guk, scaffolding, jam, tight junction, cell adhesion
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Peripheral membrane protein; Cytoplasmic side: Q07157; Cell junction, tight junction: Q9Y624
• Total number of polymer chains: 2
• Total formula weight: 46033.41

Authors

Nomme, J.,Lavie, A. (deposition date: 2011-09-13, release date: 2011-10-12, Last modification date: 2023-09-13)

Primary citation

Nomme, J.,Fanning, A.S.,Caffrey, M.,Lye, M.F.,Anderson, J.M.,Lavie, A.
The Src Homology 3 Domain Is Required for Junctional Adhesion Molecule Binding to the Third PDZ Domain of the Scaffolding Protein ZO-1.
J.Biol.Chem., 286:43352-43360, 2011

PubMed Abstract: Tight junctions are cell-cell contacts that regulate the paracellular flux of solutes and prevent pathogen entry across cell layers. The assembly and permeability of this barrier are dependent on the zonula occludens (ZO) membrane-associated guanylate kinase (MAGUK) proteins ZO-1, -2, and -3. MAGUK proteins are characterized by a core motif of protein-binding domains that include a PDZ domain, a Src homology 3 (SH3) domain, and a region of homology to guanylate kinase (GUK); the structure of this core motif has never been determined for any MAGUK. To better understand how ZO proteins organize the assembly of protein complexes we have crystallized the entire PDZ3-SH3-GUK core motif of ZO-1. We have also crystallized this core motif in complex with the cytoplasmic tail of the ZO-1 PDZ3 ligand, junctional adhesion molecule A (JAM-A) to determine how the activity of different domains is coordinated. Our study shows a new feature for PDZ class II ligand binding that implicates the two highly conserved Phe(-2) and Ser(-3) residues of JAM. Our x-ray structures and NMR experiments also show for the first time a role for adjacent domains in the binding of ligands to PDZ domains in the MAGUK proteins family.

PubMed: 22030391
DOI: 10.1074/jbc.M111.304089

Experimental method

X-RAY DIFFRACTION (2.502 Å)