The structure and function of G-protein-coupled receptors
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TLDR
G-protein-coupled receptors mediate most of the authors' physiological responses to hormones, neurotransmitters and environmental stimulants, and so have great potential as therapeutic targets for a broad spectrum of diseases.Abstract:
G-protein-coupled receptors (GPCRs) mediate most of our physiological responses to hormones, neurotransmitters and environmental stimulants, and so have great potential as therapeutic targets for a broad spectrum of diseases. They are also fascinating molecules from the perspective of membrane-protein structure and biology. Great progress has been made over the past three decades in understanding diverse GPCRs, from pharmacology to functional characterization in vivo. Recent high-resolution structural studies have provided insights into the molecular mechanisms of GPCR activation and constitutive activity.read more
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References
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Crystal Structure of Rhodopsin: A G Protein-Coupled Receptor
Krzysztof Palczewski,Takashi Kumasaka,Tetsuya Hori,Craig A. Behnke,H. Motoshima,Brian A. Fox,I. Le Trong,David C. Teller,Tetsuji Okada,Ronald E. Stenkamp,Masaki Yamamoto,Masashi Miyano +11 more
TL;DR: This article determined the structure of rhodopsin from diffraction data extending to 2.8 angstroms resolution and found that the highly organized structure in the extracellular region, including a conserved disulfide bridge, forms a basis for the arrangement of the sevenhelix transmembrane motif.
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High-Resolution Crystal Structure of an Engineered Human β2-Adrenergic G Protein–Coupled Receptor
Vadim Cherezov,Daniel M. Rosenbaum,Michael A. Hanson,Søren G. F. Rasmussen,Foon Sun Thian,Tong Sun Kobilka,Hee Jung Choi,Peter Kuhn,William I. Weis,Brian K. Kobilka,Raymond C. Stevens +10 more
TL;DR: Although the location of carazolol in the β2-adrenergic receptor is very similar to that of retinal in rhodopsin, structural differences in the ligand-binding site and other regions highlight the challenges in using rhodopin as a template model for this large receptor family.
Journal ArticleDOI
The G-Protein-Coupled Receptors in the Human Genome Form Five Main Families : Phylogenetic Analysis, Paralogon Groups, and Fingerprints
TL;DR: This study represents the first overall map of the GPCR sequences in a single mammalian genome and shows several common structural features indicating that the human GPCRs in the GRAFS families share a common ancestor.
Book ChapterDOI
[19] Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors
TL;DR: This chapter discusses the integrated methods for the construction of three-dimensional models and computational probing of structure–function relations in G protein-coupled receptors (GPCR) and expects increased rate of success achieved by molecular modeling and computational simulation methods in providing structural insights relevant to the functions of biological molecules.
Journal ArticleDOI
Crystal structure of the human beta2 adrenergic G-protein-coupled receptor.
Søren G. F. Rasmussen,Hee Jung Choi,Daniel M. Rosenbaum,Tong Sun Kobilka,Foon Sun Thian,Patricia C. Edwards,Manfred Burghammer,Venkata R. P. Ratnala,Ruslan Sanishvili,Robert F. Fischetti,Gebhard F. X. Schertler,William I. Weis,Brian K. Kobilka +12 more
TL;DR: In this paper, the human beta2 adrenoceptor (beta2AR) was crystallized in a lipid environment when bound to an inverse agonist and in complex with a Fab that binds to the third intracellular loop.
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