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Structure and Function Studies of GPCRs by Site-Specific Incorporation of Unnatural Amino Acids

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Structure and Function of GPCRs

Part of the book series: Topics in Medicinal Chemistry ((TMC,volume 30))

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Abstract

In the past decade, genetic code expansion technology has emerged as discovery tools in studies of GPCRs for monitoring of dynamic protein conformational changes, for the screening of ligand–protein and protein–protein interactions, and as alternatives to conventional labeling approaches for the site-specific labeling of GPCRs with spectroscopy probes. Interactome mapping among GPCRs, their ligands, and interactive proteins discovered using genetically encoded photo-cross-linking unnatural amino acids (Uaas) display methods that link substrate specificity to binding pockets revealed by static X-ray crystal structures are inaccessible by other methodologies. Fluorescent-based analysis to directly monitor the GPCR conformational changes are beginning to move forward into cell-based assays for high-throughput drug screening platforms. This review details the significant progress in Uaa containing GPCRs discovery platforms, as well as advances in understanding the structure activity relationship of GPCRs in the “post structural biology” era.

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Acknowledgements

We are grateful for M. Kazmi, T. He, T. Huber, and T.P. Sakmar for their supports and advice. Financial support was provided by the Chinese Scholars Council (CSC fellowship to M.T.), the Agence Nationale de la Recherche of France (ANR-JCJC grant to S.Y.), and the National Natural Science Foundation of China (31528007 to S.Y. and C.Y.).

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Authors and Affiliations

  1. Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, ECNU, Shanghai, China

    Meilin Tian & Chonggang Yuan

  2. Institut de Biologie de l’Ecole Normale Supérieure, Ecole Normale Supérieure, Paris, France

    Meilin Tian

  3. Institut National de la Santé et de la Recherche Médicale (INSERM), U1024, Paris, France

    Meilin Tian & Shixin Ye

  4. Centre National de la Recherche Scientifique (CNRS), UMR 7238, 8197, Paris, France

    Meilin Tian & Shixin Ye

  5. Origins of Cancer Program, Centenary Institute, Sydney Medical School, University of Sydney, Camperdown, NSW, Australia

    Qian Wang

  6. Laboratory of Computational and Quantitative Biology (LCQB), Institute of Biology, Paris-Seine, University of Pierre and Marie Curie, Paris, France

    Shixin Ye

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  1. Meilin Tian
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  2. Qian Wang
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  3. Chonggang Yuan
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Correspondence to Shixin Ye .

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  1. Institut de Génomique Fonctionnelle Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), University of Montpellier, Montpellier, France

    Guillaume Lebon

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Tian, M., Wang, Q., Yuan, C., Ye, S. (2017). Structure and Function Studies of GPCRs by Site-Specific Incorporation of Unnatural Amino Acids. In: Lebon, G. (eds) Structure and Function of GPCRs. Topics in Medicinal Chemistry, vol 30. Springer, Cham. https://doi.org/10.1007/7355_2017_20

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