Journal
EMBO JOURNAL
Volume 28, Issue 9, Pages 1351-1361Publisher
WILEY
DOI: 10.1038/emboj.2009.63
Keywords
cell adhesion; integrin receptors; membrane proteins; transmembrane signalling
Categories
Funding
- US National Institutes of Health [HL089726]
- MHG [HL70784, AR27214]
- American Heart Association
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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 a and beta subunits is central to these signalling events. Here, we report the structure of the integrin alpha IIb beta 3 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 alpha IIb and beta 3 TM helices. The structurally unique, highly conserved integrin aIIbb3 TM complex rationalizes bi-directional signalling and represents the first structure of a heterodimeric TM receptor complex. The EMBO Journal (2009) 28, 1351-1361. doi: 10.1038/emboj.2009.63; Published online 12 March 2009
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