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Originally published In Press as doi:10.1074/jbc.M700829200 on March 7, 2007

J. Biol. Chem., Vol. 282, Issue 18, 13160-13166, May 4, 2007
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The Contribution of Conformational Adjustments and Long-range Electrostatic Forces to the CD2/CD58 Interaction*

Alice Kearney{ddagger}1, Adam Avramovic{ddagger}, Mónica A. A. Castro§2, Alexandre M. Carmo2, Simon J. Davis§3, and P. Anton van der Merwe{ddagger}14

From the {ddagger}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

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 for publication, January 29, 2007 , and in revised form, March 7, 2007.

* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 Supported by the Medical Research Council, United Kingdom.

2 Supported by the European Regional Development Fund (FEDR) and Fundação para a Ciência e a Tecnologia.

3 Supported by the Wellcome Trust.

4 To whom correspondence should be addressed. Tel.: 44-1865-274493; Fax: 44-1865-274491; E-mail: anton.vandermerwe{at}path.ox.ac.uk.


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J. Immunol.Home page
R. J. Nunes, M. A. A. Castro, C. M. Goncalves, M. Bamberger, C. F. Pereira, G. Bismuth, and A. M. Carmo
Protein Interactions between CD2 and Lck Are Required for the Lipid Raft Distribution of CD2
J. Immunol., January 15, 2008; 180(2): 988 - 997.
[Abstract] [Full Text] [PDF]




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