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- Vsevolod Katritch
- Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037;
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- Vadim Cherezov
- Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037;
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- Raymond C. Stevens
- Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037;
説明
<jats:p> During the past few years, crystallography of G protein–coupled receptors (GPCRs) has experienced exponential growth, resulting in the determination of the structures of 16 distinct receptors—9 of them in 2012 alone. Including closely related subtype homology models, this coverage amounts to approximately 12% of the human GPCR superfamily. The adrenergic, rhodopsin, and adenosine receptor systems are also described by agonist-bound active-state structures, including a structure of the receptor–G protein complex for the β<jats:sub>2</jats:sub>-adrenergic receptor. Biochemical and biophysical techniques, such as nuclear magnetic resonance and hydrogen-deuterium exchange coupled with mass spectrometry, are providing complementary insights into ligand-dependent dynamic equilibrium between different functional states. Additional details revealed by high-resolution structures illustrate the receptors as allosteric machines that are controlled not only by ligands but also by ions, lipids, cholesterol, and water. This wealth of data is helping redefine our knowledge of how GPCRs recognize such a diverse array of ligands and how they transmit signals 30 angstroms across the cell membrane; it also is shedding light on a structural basis of GPCR allosteric modulation and biased signaling. </jats:p>
収録刊行物
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- Annual Review of Pharmacology and Toxicology
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Annual Review of Pharmacology and Toxicology 53 (1), 531-556, 2013-01-06
Annual Reviews
