10.1371/journal.pone.0089263.g005 Mariano Sanchez-Lockhart Mariano Sanchez-Lockhart Ana V. Rojas Ana V. Rojas Margaret M. Fettis Margaret M. Fettis Richard Bauserman Richard Bauserman Trissha R. Higa Trissha R. Higa Hongyu Miao Hongyu Miao Richard E. Waugh Richard E. Waugh Jim Miller Jim Miller WT CD28 adopts a bivalent binding conformation when starting from the CTLA-4 dimer orientation. Public Library of Science 2014 Biochemistry proteins Immune system proteins Protein interactions protein structure T-cell receptors Transmembrane proteins Biomacromolecule-ligand interactions Macromolecular assemblies biophysics immunology Immune cells t cells Immune response immunomodulation Molecular cell biology Signal transduction Mechanisms of signal transduction crosstalk Membrane receptor signaling Immunologic receptor signaling Signaling in cellular processes Transmembrane signaling cell adhesion Computer modeling Computerized simulations cd28 adopts bivalent binding conformation ctla-4 dimer 2014-02-24 03:32:16 Figure https://plos.figshare.com/articles/figure/_WT_CD28_adopts_a_bivalent_binding_conformation_when_starting_from_the_CTLA_4_dimer_orientation_/943319 <p>MD simulations were run with WT CD28 starting from a CTLA-4 dimer orientation. (<b>A</b>) The RMSD of three independent trajectories with respect to the initial conformation are shown over time. There is considerable rearrangement of the subunits at the beginning of the simulations, reflected by an increase in the RMSD. The conformational fluctuations stabilize after the first 100 ns of simulation, although the trajectories adopt different conformations. This instability was not inherent to this dimer orientation, as the RMSD of MD simulations of CTLA-4 remained below 4Å (data not shown). (<b>B</b>) CD80 molecules were docked onto the simulated CD28 dimers to obtain the corresponding CD28-CD80 complexes. The surface area buried between the docked ligands was calculated at various times along each of the three independent trajectories to estimate the fraction of bivalent-competent conformations; the average over all three trajectories was 79%. (<b>C</b>) A representative conformation of CD28 (green) showing docked CD80 ligands (cyan) illustrates the potential for bivalent ligand binding.</p>