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Structural Basis of Chemokine Receptor Function—A Model for Binding Affinity and Ligand Selectivity

  • Original Paper
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Bioscience Reports

Abstract

Chemokine receptors play fundamental roles in human physiology from embryogenesis to inflammatory response. The receptors belong to the G-protein coupled receptor class, and are activated by chemokine ligands with a range of specificities and affinities that result in a complicated network of interactions. The molecular basis for function is largely a black box, and can be directly attributed to the lack of structural information on the receptors. Studies to date indicate that function can be best described by a two-site model, that involves interactions between the receptor N-domain and ligand N-terminal loop residues (site-I), and between receptor extracellular loop and the ligand N-terminal residues (site-II). In this review, we describe how the two-site model could modulate binding affinity and ligand selectivity, and also highlight some of the unique chemokine receptor features, and their role in function.

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Acknowledgements

This work was supported by the National Institutes of Health, American Heart Association, and the John Sealy Endowment Grant (to K. R.), and by a McLaughlin Predoctoral Fellowship (to L. R.).

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  1. Department of Biochemistry and Molecular Biology and Sealy Center for Structural Biology, The University of Texas Medical Branch, Galveston, TX, 77555-1055, USA

    Lavanya Rajagopalan & Krishna Rajarathnam

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  1. Lavanya Rajagopalan
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  2. Krishna Rajarathnam
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Correspondence to Krishna Rajarathnam.

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Rajagopalan, L., Rajarathnam, K. Structural Basis of Chemokine Receptor Function—A Model for Binding Affinity and Ligand Selectivity. Biosci Rep 26, 325–339 (2006). https://doi.org/10.1007/s10540-006-9025-9

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  • DOI: https://doi.org/10.1007/s10540-006-9025-9

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