The structure of the integrin alphaIIbbeta3 transmembrane complex explains integrin transmembrane signalling

EMBO J. 2009 May 6;28(9):1351-61. doi: 10.1038/emboj.2009.63. Epub 2009 Mar 12.


Heterodimeric integrin adhesion receptors regulate cell migration, survival and differentiation in metazoa by communicating signals bi-directionally across the plasma membrane. Protein engineering and mutagenesis studies have suggested that the dissociation of a complex formed by the single-pass transmembrane (TM) segments of the alpha and beta subunits is central to these signalling events. Here, we report the structure of the integrin alphaIIbbeta3 TM complex, structure-based site-directed mutagenesis and lipid embedding estimates to reveal the structural event that underlies the transition from associated to dissociated states, that is, TM signalling. The complex is stabilized by glycine-packing mediated TM helix crossing within the extracellular membrane leaflet, and by unique hydrophobic and electrostatic bridges in the intracellular leaflet that mediate an unusual, asymmetric association of the 24- and 29-residue alphaIIb and beta3 TM helices. The structurally unique, highly conserved integrin alphaIIbbeta3 TM complex rationalizes bi-directional signalling and represents the first structure of a heterodimeric TM receptor complex.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Cell Membrane / metabolism*
  • Flow Cytometry
  • Humans
  • Magnetic Resonance Spectroscopy
  • Membrane Lipids / chemistry
  • Membrane Lipids / metabolism
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Platelet Glycoprotein GPIIb-IIIa Complex / chemistry*
  • Platelet Glycoprotein GPIIb-IIIa Complex / genetics
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism*
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Signal Transduction / physiology*


  • Membrane Lipids
  • Membrane Proteins
  • Platelet Glycoprotein GPIIb-IIIa Complex