Figure 1.

Structural integrity of the membrane-embedded helices throughout the MD simulations and contacts across the interface. (a) Exemplary simulation box generated to perform MD simulations including the NMR structure of α_IIbβ₃ TMD (PDB ID 2K9J; cartoon and surface representation) with the position of the OMC (red box) and IMC (brown box) indicated; phospholipids are shown as orange sticks, and water layers as blue spheres. Close-up views of the box contents show essential residues mediating the clasps: α_IIb-G972/G976 and β₃-V700/I704 for the OMC, α_IIb-F992/F993/R995 and β₃-W715/K716/D723 for the IMC plus the putative salt bridge. (b) Sequence alignment of the α_IIbβ₃, α_vβ₃, α₅β₁ TMD sequences used to generate the homology models. GXXXG and GFFKR motifs are highlighted in red and brown, respectively, and R995/D723 residues in purple. Black bars indicate the TMD borders as reported in ref.⁴⁵. (c) Two dimensional histograms of the RMSD values of all C_α atoms (ordinate values) and only those that are embedded in the membrane (abscissa values) (range of residues considered: P996-V1015 and D718-I747) calculated over three MD simulations. Blue, cornflowerblue, turquoiseblue colored dots represent α_IIbβ₃ (MD simulations 1, 2 and 3); darkgrey, black, lightgrey α_vβ₃; chocolate, orange, firebrick α₅β₁. (d,e) Histograms of the total number of overall contacts per residue at the OMC and IMC averaged over three MD simulations, with error bars showing the standard error of the mean (SEM; eq. 6) and stars indicating the statistical significance (see Methods section for definition). Here, only residues of the α subunit are shown (numbering refers to the α_IIb subunit). On the right of the plots, a superimposition of the α_IIbβ₃, α_vβ₃, and α₅β₁ TMDs in blue, grey, and orange, respectively, is shown. The C_α atoms of residues considered in the contact analysis are indicated as spheres, and the residues of the α subunit considered in the analyses are labeled.