Structure-Function of the G-protein-Coupled Receptor Superfamily

By Vsevolod Katritch, Vadim Cherezov, Raymond C. Stevens. Annual Review of Pharmacology and Toxicology, 2012

1,049 citations recorded by the source corpus.

During the past few years, crystallography of G protein-coupled receptors (GPCRs) has experienced exponential growth, resulting in structure determination of 14 distinct receptors, 7 of them in 2012 alone. Including closely related subtype homology models, this currently amounts to about 10% coverage of the GPCR superfamily. Agonist-bound active-state structures are now known for the adrenergic, rhodopsin, and adenosine receptor systems, including a structure of the receptor-G-protein complex for the β2-adrenergic receptor. Biochemical and biophysical techniques, such as nuclear magnetic resonance (NMR) and hydrogen/deuterium exchange-mass spectrometry (HDX-MS) are providing complementary insights on ligand-dependent dynamic equilibrium between different functional states. High resolution structures such as the 1.8 A adenosine A2a receptor are illistrating the receptor as allosteric machines, controlled not only by ligands, but by sodium, lipids, cholesterol, and water. This wealth of data is helping to redefine our knowledge of how GPCRs recognize such a diverse array of ligands and transmit signals 30 angstroms across the cell membrane, also shedding light on a structural basis of GPCR allosteric modulation and biased signaling.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/539d94e1ccd2159e3288f97d8a255fec2f8837e1

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

In Molecular Biology

Citations in the corpus

RCSB Protein Data Bank: Enabling biomedical research and drug discovery (2019, background): “GPCR structures have been elucidated in both active and inactive conformational states, some including bound small-molecule ligands or drugs, bound peptide/protein ligands, bound heterotrimeric G proteins, and in some cases stabilizing Fab fragments and/or camelid-nanobodies.(34) Structure-guided dr”
Integrating structural and mutagenesis data to elucidate GPCR ligand binding (2016, background): “com changes during receptor activation, allosteric modulation by ligands, ions and lipids, cholesterol, as well as G protein binding [5 ,6 ,7].”
Generic GPCR Residue Numbers - Aligning Topology Maps Minding The Gaps (2014, background): “, Katritch, V., Marshall, F. H., ... Gloriam, D. E. (2015). Generic GPCR residue numbers - aligning topology maps while minding the gaps.”
Neutrophils to the ROScue: Mechanisms of NADPH Oxidase Activation and Bacterial Resistance (2017, background): “The binding of agonists to the extracellular domain of a GPCR stabilizes the active conformation of the receptor (Katritch et al., 2013; Ghosh et al., 2015), which in turn triggers the exchange of GDP for GTP by the G proteins.”
Structural Features for Functional Selectivity at Serotonin Receptors (2013, background): “At the cytoplasmic side of the receptors, GPCR activation is generally characterized by the displacement of helices V, VI, and VII (10).”
Antibody Structure and Function: The Basis for Engineering Therapeutics (2019, background): “Recent crystal structures have shown that there is limited access to epitopes due to the presence of N-terminal domain glycosylation and limited surface exposure to the extracellular membrane protein loops [292].”
GPCRdb: the G protein‐coupled receptor database – an introduction (2016, background): “2196 British Journal of Pharmacology (2016) 173 2195–2207 and T/taste2 and have revealed common conformational changes during receptor activation, allosteric modulation by ions, lipids, cholesterol, and water; as well as G protein binding (Katritch et al., 2013; Venkatakrishnan et al., 2013; Tehan e”
Structural Basis for Ligand Recognition and Functional Selectivity at Angiotensin Receptor*♦ (2015, background): “It is highly conserved in many other class A GPCRs, explaining allosteric sodium effects observed for many of these receptors (37).”