Abstract
Tensin is a protein confined at those discrete and specialized regions of the plasma membrane, known as focal adhesions. It contains, at the Cโterminus, a phosphotyrosine binding (PTB) domain that can interact with the cytoplasmic tail of ฮฒโintegrins and is necessary for localization of the protein to cellโmatrix adhesions. Here, we present the NMR solution structure of the PTB domain of tensin1. Moreover, through NMR binding studies, we demonstrate that the PTB domain of tensin1 is able to interact with phosphatidylinositol 4, 5โdiphosphate (PtIns(4,5)P2) and phosphatidylinositol 4โphosphate (PtIns(4)P), presenting higher affinity for the diphosphorylated inositide. Chemical shift mapping studies reveal a putative PtIns(4,5)P2 binding region that is distinct from the predicted integrin ฮฒโtail recognition site. Heteronuclear NOE experiments, recorded in absence and presence of PtIns(4,5)P2, indicate that the interaction with lipids decreases the flexibility of loop regions, predicted to be important for integrin binding, and thus, proposes a possible correlation between the two distinct binding events. Therefore, our studies suggest that capture of lipids by the PTB domain of tensin1 may play a role for the protein function at focal adhesions. ยฉ 2007 Wiley Periodicals, Inc. Biopolymers 89: 86โ92, 2008.
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