The contribution of conformational adjustments and long-range electrostatic forces to the CD2/CD58 interaction
Kearney A, Avramovic A, Castro MA, Carmo AM, Davis SJ, van der Merwe PA. (2007), J Biol Chem. 282, 13160-6
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.
Key figure: The dependence of binding on ionic strength
The dependence of KD (A), and kon (B and C) on the concentration of NaCl or KF (40) is shown. The KD was measured directly, whereas konwas calculated from the relationship kon = koff/KD following direct measurement of koff. The error bars indicate S.E. (n ≥ 3) and were determined by error propagation for kon.