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Mutation Analysis of Receptors and Relationship of Receptor Usage to Disease

  • Chapter
Chemokines in Disease

Part of the book series: Contemporary Immunology ((CONTIM))

  • 65 Accesses

Abstract

Pioneering protein engineering work by Kobilka et al. utilized chimeric constructs between α- and β-adrenergic receptors, and mutant receptors with partial deletions to identify domains involved in G-protein coupling and specific ligand binding (1). Since then, this method has been employed extensively in structure-function studies of many different G-protein-coupled, seven transmembrane domain (7TMD) receptors (reviewed in ref. 2). Recent application of the technique to the analysis of the interleukin-8 chemokine receptors, IL-8RA and IL8-RB, has served to indicate that the receptor-ligand interaction can be highly complex, with multiple domains contributing to ligand binding and, independently, to signal transduction (3). On the other hand, study of the Duffy antigen receptor for chemokines (DARC) suggests that chemokine binding by this promiscuous molecule is primarily localized to the first extracellular (N-terminal) domain (4,5). Comparison of amino acid sequence and function between coreceptor homologs of different species can highlight conserved regions likely to be involved in ligand binding and signal transduction (5). A strategy of specifically modifying individual or small groups of charged residues has also been employed to assess structure and function of 7TMD receptors. Such site-directed mutagenesis of the type A IL-8 receptor has been used to demonstrate that certain residues in the N-terminal domain and third extracellular loop are critical for ligand binding (6,7).

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Authors
  1. Emma J. Aarons
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  2. Richard A. Koup
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  1. Genentech, South San Francisco, CA, USA

    Caroline A. Hébert PhD (Senior Scientist) (Senior Scientist)

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© 1999 Springer Science+Business Media New York

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Aarons, E.J., Koup, R.A. (1999). Mutation Analysis of Receptors and Relationship of Receptor Usage to Disease. In: Hébert, C.A. (eds) Chemokines in Disease. Contemporary Immunology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-706-2_18

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  • DOI: https://doi.org/10.1007/978-1-59259-706-2_18

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-4762-1

  • Online ISBN: 978-1-59259-706-2

  • eBook Packages: Springer Book Archive

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