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Dimerization of transmembrane (TM) α helices of membrane receptors plays a key role in signaling. We show that molecular dynamics simulations yield models of integrin TM helix heterodimers, which agree well with available NMR structures. We use a multiscale simulation approach, combining coarse-grained and subsequent atomistic simulation, to model the dimerization of wild-type (WT) and mutated sequences of the αIIb and β3 integrin TM helices. The WT helices formed a stable, right-handed dimer with the same helix-helix interface as in the published NMR structure (PDB: 2K9J). In contrast, the presence of disruptive mutations perturbed the interface between the helices, altering the conformational stability of the dimer. The αIIb/β3 interface was more flexible than that of, e.g., glycophorin A. This is suggestive of a role for alternative packing modes of the TM helices in transbilayer signaling.

Original publication




Journal article



Publication Date





1477 - 1484


Amino Acid Sequence, Animals, Cell Membrane, Computer Simulation, Integrin beta3, Lipid Bilayers, Magnetic Resonance Spectroscopy, Mammals, Membrane Proteins, Models, Molecular, Molecular Sequence Data, Mutation, Platelet Membrane Glycoprotein IIb, Protein Multimerization, Protein Stability, Protein Structure, Secondary, Signal Transduction