4YYX

Crystal structure of the ZO-1 PDZ1 domain in complex with the 7-mer Claudin2 C-terminal tail

Replaces:  4OEQ

Summary for 4YYX

• Entry DOI: 10.2210/pdb4yyx/pdb
• Related: 4OEO 4OEP
• Descriptor: Tight junction protein ZO-1 fused with Claudin-2 C-terminal, FORMIC ACID (3 entities in total)
• Functional Keywords: tight junction, maguk, pdz1, scaffolding, cell adhesion, claudin
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 23133.99

Authors

Nomme, J.,Lavie, A. (deposition date: 2015-03-24, release date: 2015-04-01, Last modification date: 2023-09-27)

Primary citation

Nomme, J.,Antanasijevic, A.,Caffrey, M.,Van Itallie, C.M.,Anderson, J.M.,Fanning, A.S.,Lavie, A.
Structural Basis of a Key Factor Regulating the Affinity between the Zonula Occludens First PDZ Domain and Claudins.
J.Biol.Chem., 290:16595-16606, 2015

PubMed Abstract: The molecular seal between epithelial cells, called the tight junction (TJ), is built by several membrane proteins, with claudins playing the most prominent role. The scaffold proteins of the zonula occludens family are required for the correct localization of claudins and hence formation of the TJ. The intracellular C terminus of claudins binds to the N-terminal PDZ domain of zonula occludens proteins (PDZ1). Of the 23 identified human claudin proteins, nine possess a tyrosine at the -6 position. Here we show that the claudin affinity for PDZ1 is dependent on the presence or absence of this tyrosine and that the affinity is reduced if the tyrosine is modified by phosphorylation. The PDZ1 β2-β3 loop undergoes a significant conformational change to accommodate this tyrosine. Cell culture experiments support a regulatory role for this tyrosine. Plasticity has been recognized as a critical property of TJs that allow cell remodeling and migration. Our work provides a molecular framework for how TJ plasticity may be regulated.

PubMed: 26023235
DOI: 10.1074/jbc.M115.646695

Experimental method

X-RAY DIFFRACTION (1.79 Å)