Structure of the PTB domain of tensin1 and a model for its recruitment to fibrillar adhesions

Tensin is a cytoskeletal protein that links integrins to the actin cytoskeleton at sites of cell‐matrix adhesion. Here we describe the crystal structure of the phosphotyrosine‐binding (PTB) domain of tensin1, and show that it binds integrins in an NPxY‐dependent fashion. Alanine mutagenesis of both the PTB domain and integrin tails supports a model of integrin binding similar to that of the PTB‐like domain of talin. However, we also show that phosphorylation of the NPxY tyrosine, which disrupts talin binding, has a negligible effect on tensin binding. This suggests that tyrosine phosphorylation of integrin, which occurs during the maturation of focal adhesions, could act as a switch to promote the migration of tensin–integrin complexes into fibronectin‐mediated fibrillar adhesions.