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>