A coiled-coil structure of the alphaIIbbeta3 integrin transmembrane and cytoplasmic domains in its resting state.

One of the hallmark features of the integrin receptors is the ability to transmit signals bidirectionally through the cell membrane. The transmembrane integrin domains are pivotal to the signaling events. An understanding of the signaling mechanism requires structural information. Here, we report a structural model of the transmembrane and part of the cytosolic domains of the alphaIIbbeta3 integrin in its resting state. The model was obtained computationally by a restrained conformational search of helix-helix interactions. It agrees with one published NMR structure of the cytoplasmic complex and can put many experimental findings on structural grounds. According to our model, integrins form an intricately designed coiled-coil structure in the resting state. The conserved Glycophorin A (GpA)-like sequence motif of the alpha, but not the beta, subunit, is in the interface of this model. Based on our calculations and other data, a signaling mechanism that involves a transient GpA-like structure is proposed.