3LH5

Crystal Structure of the SH3-Guanylate kinase core domain of ZO-1

Summary for 3LH5

• Entry DOI: 10.2210/pdb3lh5/pdb
• Descriptor: Tight junction protein ZO-1 (2 entities in total)
• Functional Keywords: zo-1, sh3-guanylate kinase, intramolecular fold, cell junction, cell membrane, membrane, phosphoprotein, sh3 domain, tight junction, protein binding
• Biological source: Homo sapiens; More
• Cellular location: Cell membrane; Peripheral membrane protein; Cytoplasmic side: Q07157
• Total number of polymer chains: 1
• Total formula weight: 29047.04

Authors

Lye, M.F.,Lavie, A. (deposition date: 2010-01-21, release date: 2010-03-02, Last modification date: 2024-02-21)

Primary citation

Lye, M.F.,Fanning, A.S.,Su, Y.,Anderson, J.M.,Lavie, A.
Insights into regulated ligand binding sites from the structure of ZO-1 Src homology 3-guanylate kinase module.
J.Biol.Chem., 285:13907-13917, 2010

PubMed Abstract: Tight junctions are dynamic components of epithelial and endothelial cells that regulate the paracellular transport of ions, solutes, and immune cells. The assembly and permeability of these junctions is dependent on the zonula occludens (ZO) proteins, members of the membrane-associated guanylate kinase homolog (MAGUK) protein family, which are characterized by a core Src homology 3 (SH3)-GUK module that coordinates multiple protein-protein interactions. The structure of the ZO-1 SH3-GUK domain confirms that the interdependent folding of the SH3 and GUK domains is a conserved feature of MAGUKs, but differences in the orientation of the GUK domains in three different MAGUKs reveal interdomain flexibility of the core unit. Using pull-down assays, we show that an effector loop, the U6 region in ZO-1, forms a novel intramolecular interaction with the core module. This interaction is divalent cation-dependent and overlaps with the binding site for the regulatory molecule calmodulin on the GUK domain. These findings provide insight into the previously observed ability of the U6 region to regulate TJ assembly in vivo and the structural basis for the complex protein interactions of the MAGUK family.

PubMed: 20200156
DOI: 10.1074/jbc.M109.093674

Experimental method

X-RAY DIFFRACTION (2.6 Å)