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Molecular signatures of G-protein-coupled receptors
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Journal Article
Molecular signatures of G-protein-coupled receptors
2013
Overview
A systematic investigation of high-resolution G-protein-coupled receptor (GPCR) structures uncovers a conserved inter-helical network of non-covalent contacts that defines the GPCR fold, and provides insights into the molecular determinants of different GPCR conformations.
Comparative analysis of GPCRs
Understanding the conformational states of G-protein-coupled receptors (GPCRs) has been an area of intense research in recent years. GPCRs are membrane proteins that act as sensors for a broad range of extracellular signals, including photons, ions, small organic molecules, and even entire proteins. Approximately one-third of all known drugs target GPCRs, including small molecule therapeutics used to treat cardiac malfunction, asthma and migraines. This Review reports a systematic analysis of all known high-resolution GPCR structures and provides insights into the molecular determinants of different GPCR conformations. Understanding how these membrane proteins function at the molecular level should facilitate the development of subtype-selective, highly efficacious therapeutics.
G-protein-coupled receptors (GPCRs) are physiologically important membrane proteins that sense signalling molecules such as hormones and neurotransmitters, and are the targets of several prescribed drugs. Recent exciting developments are providing unprecedented insights into the structure and function of several medically important GPCRs. Here, through a systematic analysis of high-resolution GPCR structures, we uncover a conserved network of non-covalent contacts that defines the GPCR fold. Furthermore, our comparative analysis reveals characteristic features of ligand binding and conformational changes during receptor activation. A holistic understanding that integrates molecular and systems biology of GPCRs holds promise for new therapeutics and personalized medicine.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 631/535
/ Animals
/ Biochemistry, Molecular Biology
/ Biology
/ Disease
/ Genomes
/ Hormones
/ Humanities and Social Sciences
/ Humans
/ Ligands
/ Peptides
/ Proteins
/ Receptors, G-Protein-Coupled - agonists
/ Receptors, G-Protein-Coupled - antagonists & inhibitors
/ Receptors, G-Protein-Coupled - chemistry
/ Receptors, G-Protein-Coupled - metabolism
/ Science
/ Studies
