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

229 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
Externally publishedYes

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Integrins
Mutagenesis
Protein Engineering
Cell membranes
Site-Directed Mutagenesis
Static Electricity
Glycine
Cell Movement
Cell Differentiation
Electrostatics
Cell Survival
Cell Membrane
Association reactions
Membranes
Lipids
Proteins
adhesion receptor

ASJC Scopus subject areas

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

Cite this

The structure of the integrin αiIbΒ3 transmembrane complex explains integrin transmembrane signalling. / Lau, Tong Lay; Kim, Chungho; Ginsberg, Mark H.; Ulmer, Tobias S.

In: EMBO Journal, Vol. 28, No. 9, 06.05.2009, p. 1351-1361.

Research output: Contribution to journalArticle

Lau, Tong Lay ; Kim, Chungho ; Ginsberg, Mark H. ; Ulmer, Tobias S. / The structure of the integrin αiIbΒ3 transmembrane complex explains integrin transmembrane signalling. In: EMBO Journal. 2009 ; Vol. 28, No. 9. pp. 1351-1361.
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