3tsz | pdb_00003tsz
crystal structure of PDZ3-SH3-GUK core module from human ZO-1 in complex with 12mer peptide from human JAM-A cytoplasmic tail
Structural highlights
Function[ZO1_HUMAN] The N-terminal may be involved in transducing a signal required for tight junction assembly, while the C-terminal may have specific properties of tight junctions. The alpha domain might be involved in stabilizing junctions. Plays a role in the regulation of cell migration by targeting CDC42BPB to the leading edge of migrating cells.[1] [JAM1_HUMAN] Seems to play a role in epithelial tight junction formation. Appears early in primordial forms of cell junctions and recruits PARD3. The association of the PARD6-PARD3 complex may prevent the interaction of PARD3 with JAM1, thereby preventing tight junction assembly (By similarity). Plays a role in regulating monocyte transmigration involved in integrity of epithelial barrier. Involved in platelet activation. In case of orthoreovirus infection, serves as receptor for the virus. Publication Abstract from PubMedTight 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 is 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. The Src Homology 3 Domain is Required for Junctional Adhesion Molecule Binding to the Third PDZ Domain of the Scaffolding Protein ZO-1.,Nomme J, Fanning AS, Caffrey M, Lye MF, Anderson JM, Lavie A J Biol Chem. 2011 Oct 26. PMID:22030391[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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