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

Protein Sci. 2007 Jun;16(6):1223-9. doi: 10.1110/ps.072798707. Epub 2007 May 1.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chickens
  • Crystallography, X-Ray
  • Integrins / chemistry
  • Integrins / genetics
  • Integrins / metabolism
  • Microfilament Proteins / chemistry*
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Molecular Sequence Data
  • Phosphorylation
  • Phosphotyrosine / chemistry
  • Phosphotyrosine / genetics
  • Phosphotyrosine / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Talin / chemistry
  • Talin / genetics
  • Talin / metabolism
  • Tensins
  • Tyrosine / chemistry
  • Tyrosine / genetics
  • Tyrosine / metabolism

Substances

  • Integrins
  • Microfilament Proteins
  • Talin
  • Tensins
  • Phosphotyrosine
  • Tyrosine

Associated data

  • PDB/1WVH