The Dynamic Process of β2-Adrenergic Receptor Activation
نویسندگان
چکیده
منابع مشابه
The Dynamic Process of β2-Adrenergic Receptor Activation
G-protein-coupled receptors (GPCRs) can modulate diverse signaling pathways, often in a ligand-specific manner. The full range of functionally relevant GPCR conformations is poorly understood. Here, we use NMR spectroscopy to characterize the conformational dynamics of the transmembrane core of the β(2)-adrenergic receptor (β(2)AR), a prototypical GPCR. We labeled β(2)AR with (13)CH(3)ε-methion...
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A third of marketed drugs act by binding to a G-protein-coupled receptor (GPCR) and either triggering or preventing receptor activation. Although recent crystal structures have provided snapshots of both active and inactive functional states of GPCRs, these structures do not reveal the mechanism by which GPCRs transition between these states. Here we propose an activation mechanism for the β(2)...
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G-protein-coupled receptors (GPCRs) transduce signals from the extracellular environment to intracellular proteins. To gain structural insight into the regulation of receptor cytoplasmic conformations by extracellular ligands during signaling, we examine the structural dynamics of the cytoplasmic domain of the β2-adrenergic receptor (β2AR) using (19)F-fluorine NMR and double electron-electron r...
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The β(2)-adrenergic receptor (β(2)AR) agonists with reduced tachyphylaxis may offer new therapeutic agents with improved tolerance profile. However, receptor desensitization assays are often inferred at the single signaling molecule level, thus ligand-directed desensitization is poorly understood. Here we report a label-free biosensor whole cell assay with microfluidics to determine ligand-dire...
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The natural variant C491T (rs1800088) in ADRB2 gene substitutes Threonine to Isoleucine at 164th position in β2AR and results in receptor sequestration and altered binding of agonists. Present investigation pursues to identify the effect of T164I variation on function and structure of β2AR through systematic computational approaches. The study, in addition, addresses altered binding of salbutam...
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ژورنال
عنوان ژورنال: Cell
سال: 2013
ISSN: 0092-8674
DOI: 10.1016/j.cell.2013.01.008