The structure of the integrin αiIbΒ3 transmembrane complex explains integrin transmembrane signalling

Tong Lay Lau, Chungho Kim, Mark H. Ginsberg, Tobias S. Ulmer

Research output: Contribution to journalArticle

241 Citations (Scopus)

Abstract

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 α and Β subunits is central to these signalling events. Here, we report the structure of the integrin αIIbΒ3 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 αIIb and Β3 TM helices. The structurally unique, highly conserved integrin αIIbΒ3 TM complex rationalizes bi-directional signalling and represents the first structure of a heterodimeric TM receptor complex.

Original languageEnglish
Pages (from-to)1351-1361
Number of pages11
JournalEMBO Journal
Volume28
Issue number9
DOIs
Publication statusPublished - 2009 May 6

Keywords

  • Cell adhesion
  • Integrin receptors
  • Membrane proteins
  • Transmembrane signalling

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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