The molecular basis of filamin binding to integrins and competition with talin

Mol Cell. 2006 Feb 3;21(3):337-47. doi: 10.1016/j.molcel.2006.01.011.


The ability of adhesion receptors to transmit biochemical signals and mechanical force across cell membranes depends on interactions with the actin cytoskeleton. Filamins are large, actin-crosslinking proteins that connect multiple transmembrane and signaling proteins to the cytoskeleton. Here, we describe the high-resolution structure of an interface between filamin A and an integrin adhesion receptor. When bound, the integrin beta cytoplasmic tail forms an extended beta strand that interacts with beta strands C and D of the filamin immunoglobulin-like domain (IgFLN) 21. This interface is common to many integrins, and we suggest it is a prototype for other IgFLN domain interactions. Notably, the structurally defined filamin binding site overlaps with that of the integrin-regulator talin, and these proteins compete for binding to integrin tails, allowing integrin-filamin interactions to impact talin-dependent integrin activation. Phosphothreonine-mimicking mutations inhibit filamin, but not talin, binding, indicating that kinases may modulate this competition and provide additional means to control integrin functions.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Calpain / metabolism
  • Contractile Proteins / chemistry*
  • Contractile Proteins / genetics
  • Contractile Proteins / metabolism*
  • Crystallography, X-Ray
  • Filamins
  • Integrin beta Chains / chemistry
  • Integrin beta Chains / metabolism*
  • Mice
  • Microfilament Proteins / chemistry*
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • NIH 3T3 Cells
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Reproducibility of Results
  • Sequence Homology, Amino Acid
  • Talin / metabolism*


  • Contractile Proteins
  • Filamins
  • Integrin beta Chains
  • Microfilament Proteins
  • Recombinant Fusion Proteins
  • Talin
  • Calpain

Associated data

  • PDB/2BRQ