[Show abstract][Hide abstract] ABSTRACT: CD2 is a T cell surface molecule that enhances T and natural killer cell function by binding its ligands CD58 (humans) and
CD48 (rodents) on antigen-presenting or target cells. Here we show that the CD2/CD58 interaction is enthalpically driven and
accompanied by unfavorable entropic changes. Taken together with structural studies, this indicates that binding is accompanied
by energetically significant conformational adjustments. Despite having a highly charged binding interface, neither the affinity
nor the rate constants of the CD2/CD58 interaction were affected by changes in ionic strength, indicating that long-range
electrostatic forces make no net contribution to binding.
Journal of Biological Chemistry 05/2007; 282(18):13160-13166. · 4.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study describes quantitative investigations of the impact of single charge mutations on equilibrium binding, kinetics, and the adhesion strength of the CD2-CD58 interaction. Previously steered molecular dynamics simulations guided the selection of the charge mutants investigated, which include the CD2 mutants D31A, K41A, K51A, and K91A. This set includes mutations in which the previous cell aggregation and binding data either agreed or disagreed with the steered molecular dynamics predictions. Surface plasmon resonance measurements quantified the solution binding properties. Adhesion was quantified with the surface force apparatus, which was used previously to study the closely related CD2-CD48 interaction. The results reveal roles that these salt bridges play in equilibrium binding and adhesion. We discuss both the molecular basis of this behavior and its implications for cell adhesion.
Journal of Biological Chemistry 03/2007; 282(8):5589-96. · 4.65 Impact Factor