101,916 research outputs found
Kinetics and mechanism of G protein-coupled receptor activation
No full textThe activation of a G protein-coupled receptor is generally triggered by binding of an agonist to the receptor's binding pocket, or, in the case of rhodopsin, by light-induced changes of the pre-bound retinal. This is followed by a series of a conformational changes towards an active receptor conformation, which is capable of signalling to G proteins and other downstream proteins. In the past few years, a number of new techniques have been employed to analyze the kinetics of this activation process, including X-ray crystallographic three-dimensional structures of receptors in the inactive and the active states, NMR studies of labelled receptors, molecular simulations, and optical analyses with fluorescence resonance energy transfer (FRET). Here we review our current understanding of the activation process of GPCRs as well as open questions in the sequence of events ranging from (sub-)microsecond activation by light or agonist binding to millisecond activation of receptors by soluble ligands and the subsequent generation of an intracellular signal
Random Dynamic Approach for Fragility Curves of Linear MDoF System Subjected to Earthquakes
No full textEfficacia della somministrazione di desametasone nella prevenzione degli effetti collaterali dopo avulsione chirurgica dei terzi molari inclusi
No full textModel Organisms in G Protein–Coupled Receptor Research
No full textThe study of G protein–coupled receptors (GPCRs) has benefited greatly from experimental approaches that interrogate their functions in controlled, artificial environments. Working in vitro, GPCR receptorologists discovered the basic biologic mechanisms by which GPCRs operate, including their eponymous capacity to couple to G proteins; their molecular makeup, including the famed serpentine transmembrane unit; and ultimately, their three-dimensional structure. Although the insights gained from working outside the native environments of GPCRs have allowed for the collection of low-noise data, such approaches cannot directly address a receptor’s native (in vivo) functions. An in vivo approach can complement the rigor of in vitro approaches: as studied in model organisms, it imposes physiologic constraints on receptor action and thus allows investigators to deduce the most salient features of receptor function. Here, we briefly discuss specific examples in which model organisms have successfully contributed to the elucidation of signals controlled through GPCRs and other surface receptor systems. We list recent examples that have served either in the initial discovery of GPCR signaling concepts or in their fuller definition. Furthermore, we selectively highlight experimental advantages, shortcomings, and tools of each model organism
Real-Time Monitoring of GPCR/cAMP Signalling by FRET and Single-Molecule Microscopy
No full textG-protein-coupled receptors (GPCRs), located on the surface of virtually every cell in our organism, mediate the effects of many hormones and neurotransmitters. Although GPCRs have been extensively studied for more than 4 decades using pharmacological and biochemical methods, the recent introduction of optical methods such as fluorescence resonance energy transfer (FRET) and single-molecule microscopy is fostering novel and important discoveries in the field. Here, we review the use of such optical methods, focusing on some recent examples of their application to important and still unresolved questions concerning the spatial organisation and dynamics of GPCR signalling
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