The structure of the C-terminal actin-binding domain of talin

EMBO J. 2008 Jan 23;27(2):458-69. doi: 10.1038/sj.emboj.7601965. Epub 2007 Dec 20.


Talin is a large dimeric protein that couples integrins to cytoskeletal actin. Here, we report the structure of the C-terminal actin-binding domain of talin, the core of which is a five-helix bundle linked to a C-terminal helix responsible for dimerisation. The NMR structure of the bundle reveals a conserved surface-exposed hydrophobic patch surrounded by positively charged groups. We have mapped the actin-binding site to this surface and shown that helix 1 on the opposite side of the bundle negatively regulates actin binding. The crystal structure of the dimerisation helix reveals an antiparallel coiled-coil with conserved residues clustered on the solvent-exposed face. Mutagenesis shows that dimerisation is essential for filamentous actin (F-actin) binding and indicates that the dimerisation helix itself contributes to binding. We have used these structures together with small angle X-ray scattering to derive a model of the entire domain. Electron microscopy provides direct evidence for binding of the dimer to F-actin and indicates that it binds to three monomers along the long-pitch helix of the actin filament.

Publication types

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

MeSH terms

  • Actins / metabolism*
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Crystallography, X-Ray
  • Dimerization
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Spectroscopy
  • Mice
  • Microscopy, Electron, Scanning
  • Models, Biological
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Rabbits
  • Recombinant Proteins / chemistry*
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / ultrastructure
  • Talin / chemistry*
  • Talin / genetics
  • Talin / metabolism


  • Actins
  • Peptide Fragments
  • Recombinant Proteins
  • Talin