Structure of the Integrin αIIb Transmembrane SegmentS

Integrin cell-adhesion receptors transduce signals bidirectionally across the plasma membrane via the single-pass transmembrane segments of each α and β subunit. While the β3 transmembrane segment consists of a linear 29-residue α-helix, the structure of the αIIb transmembrane segment reveals a linear 24-residue α-helix (Ile-966 -Lys-989) followed by a backbone reversal that packs Phe-992-Phe-993 against the transmembrane helix. The length of the αIIb transmembrane helix implies the absence of a significant transmembrane helix tilt in contrast to its partnering β3 subunit. Sequence alignment shows Gly-991-Phe-993 to be fully conserved among all 18 human integrin α subunits, suggesting that their unusual structural motif is prototypical for integrin α subunits. The αIIb 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 αIIb-β3 association, i.e. integrin transmembrane signaling.