WT CD28 can adopt a stable conformation that would allow bivalent binding.
MD simulations were run with WT CD28 starting from a rotated dimer orientation predicted from the simulations starting from the CTLA-4 dimer orientation. (A) The RMSD with respect to the initial conformation for three independent trajectories indicate that these dimer conformers are very stable. (B) When CD80 molecules were docked onto the conformations, there was no surface buried between the ligands, indicating that all conformations were bivalent. A representative bivalent conformation of CD28 (green) with docked CD80 molecules (cyan) is shown to illustrate the CD28 dimer (C) and in a rotated view to show the orientation of the docked CD80 molecules (D).