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.
McCleverty
Clare J
CJ
Cancer Center, Burnham Institute for Medical Research, La Jolla, California 92037, USA.
Lin
Diane C
DC
Liddington
Robert C
RC
D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D018360:Crystallography, X-Ray; D016023:Integrins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008840:Microfilament Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D016608:Talin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000070876:Tensins; D014443:Tyrosine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D016023:Integrins; D008840:Microfilament Proteins; D016608:Talin; D000070876:Tensins; D019000:Phosphotyrosine; D014443:Tyrosine