Talin–integrin beta cytoplasmic tail interface (Talin–β-integrin interface) (Talin–β-integrin interface)

The Talin–β-integrin interface is a critical protein-protein interaction (PPI) site responsible for the "inside-out" activation of integrin receptors (Nature Reviews Molecular Cell Biology, 2009). Talin, a large cytosolic protein, binds via its F3 phosphotyrosine-binding (PTB)-like domain to the cytoplasmic tail of the β-integrin subunit, specifically at the NPxY motif (UniProt, 2024). This binding event triggers a conformational change in the integrin's extracellular domain, shifting it from a low-affinity to a high-affinity state for ligand binding (Science, 2007). This process is fundamental to cell adhesion, migration, and mechanotransduction across various cell types, including platelets and leukocytes (Journal of Cell Science, 2013). In pathology, over-activation or overexpression of this interface contributes to thrombus formation, tumor metastasis, and inflammatory disorders (Blood, 2007; Cancer Research, 2011). Consequently, the Talin–β-integrin interface has emerged as a promising therapeutic target for developing PPI inhibitors, such as the small molecule mP13, which can modulate integrin activity more selectively than traditional extracellular antagonists (Journal of Medicinal Chemistry, 2014).

Other names

Talin–integrin beta cytoplasmic tail interactionTalin-FERM–integrin tail complexTalin-1–ITGB3 interfaceTalin-1–integrin beta-3 interaction

Inhibition of the protein-protein interaction between the Talin F3 domain and the β-integrin cytoplasmic tail, preventing inside-out integrin activation (Science, 2007; Journal of Medicinal Chemistry, 2014).