Structure of the integrin αIIb transmembrane segment

Integrin cell-adhesion receptors transduce signals bidirectionally across the plasma membrane via the single-pass transmembrane segments of each alpha and beta subunit. While the beta 3 transmembrane segment consists of a linear 29-residue alpha-helix, the structure of the alpha IIb transmembrane segment reveals a linear 24-residue alpha-helix (Ile-966-Lys-989) followed by a backbone reversal that packs Phe-992-Phe-993 against the transmembrane helix. The length of the alpha IIb transmembrane helix implies the absence of a significant transmembrane helix tilt in contrast to its partnering beta 3 subunit. Sequence alignment shows Gly-991-Phe-993 to be fully conserved among all 18 human integrin alpha subunits, suggesting that their unusual structural motif is prototypical for integrin alpha subunits. The alpha IIb transmembrane structure demonstrates a level of complexity within the membrane that is beyond simple transmembrane helices and forms the structural basis for assessing the extent of structural and topological rearrangements upon alpha IIb-beta 3 association, i.e. integrin transmembrane signaling.