Tight junction protein 1 (TJP1) PDZ2 domain (ZO-1 PDZ2)

Tight junction protein 1 (TJP1), also known as Zonula occludens-1 (ZO-1), is a large scaffolding protein essential for the formation and maintenance of tight junctions in epithelial and endothelial cells (UniProt P39447). The PDZ2 domain is the second of three PDZ domains within the protein and is uniquely characterized by its ability to form homodimers and interact with the carboxyl-terminus of Connexin 43 (Cx43) (PMID: 16880203, PMID: 21903831). This domain plays a pivotal role in coordinating the spatial organization of transmembrane proteins and linking them to the actin cytoskeleton, thereby regulating paracellular permeability and cell-cell communication (PMID: 9792670). In clinical contexts, the ZO-1 PDZ2 domain is a target for modulating barrier function; for instance, its interaction with Cx43 is targeted by the therapeutic peptide ACT1 to enhance wound healing and reduce inflammation (PMID: 16880203). Dysregulation of this domain is associated with various pathologies, including cancer metastasis, where the breakdown of tight junctions facilitates cell migration, and ischemic stroke, where blood-brain barrier integrity is lost (PMID: 25663614). Pharmacological intervention typically focuses on small molecules or peptidomimetics designed to disrupt specific protein-protein interactions mediated by the PDZ2 fold.

Other names

Zonula occludens-1 PDZ2 domainTJP1 PDZ2ZO1 PDZ2Tight junction protein ZO-1 PDZ2 domain

Inhibition of protein-protein interactions (PPI) between the PDZ2 domain and its ligands, such as Connexin 43.