The Src Homology 3 Domain Is Required for Junctional Adhesion Molecule Binding to the Third PDZ Domain of the Scaffolding Protein ZO-1
Journal Article
·
· Journal of Biological Chemistry
- NIH
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{sup -2} and Ser{sup -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.
- Research Organization:
- Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
- Sponsoring Organization:
- UNIVERSITYNIH
- OSTI ID:
- 1033778
- Journal Information:
- Journal of Biological Chemistry, Journal Name: Journal of Biological Chemistry Journal Issue: 50 Vol. 286; ISSN JBCHA3; ISSN 0021-9258
- Country of Publication:
- United States
- Language:
- ENGLISH
Similar Records
Insights into Regulated Ligand Binding Sites from the Structure of ZO-1 Src Homology 3-Guanylate Kinase Module
Structures of the human Pals1 PDZ domain with and without ligand suggest gated access of Crb to the PDZ peptide-binding groove
DLG1: Chromosome location of the closest human homologue of the Drosophila discs large tumor suppressor gene
Journal Article
·
Mon Nov 08 23:00:00 EST 2010
· J. Biol. Chem.
·
OSTI ID:1002626
Structures of the human Pals1 PDZ domain with and without ligand suggest gated access of Crb to the PDZ peptide-binding groove
Journal Article
·
Sat Feb 28 23:00:00 EST 2015
· Acta Crystallographica. Section D: Biological Crystallography
·
OSTI ID:22347722
DLG1: Chromosome location of the closest human homologue of the Drosophila discs large tumor suppressor gene
Journal Article
·
Sat Dec 09 23:00:00 EST 1995
· Genomics
·
OSTI ID:437183