The Contribution of Conformational Adjustments and Long-range Electrostatic Forces to the CD2/CD58 Interaction*
- Alice Kearney‡,1,
- Adam Avramovic‡,
- Mónica A. A. Castro§¶,2,
- Alexandre M. Carmo¶,2,
- Simon J. Davis§,3 and
- P. Anton van der Merwe‡,1,4
- ‡Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom, §Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom, and ¶Group of Cell Activation and Gene Expression, Instituto de Biologia Molecular e Celular and Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, 4099-002 Porto, Portugal
- ↵4 To whom correspondence should be addressed. Tel.: 44-1865-274493; Fax: 44-1865-274491; E-mail: anton.vandermerwe{at}path.ox.ac.uk.
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.
- Received January 29, 2007.
- Revision received March 7, 2007.
- The American Society for Biochemistry and Molecular Biology, Inc.
