[HTML][HTML] Biophysical detection of diversity and bias in GPCR function

WC Jaeger, SP Armstrong, SJ Hill… - Frontiers in …, 2014 - frontiersin.org
WC Jaeger, SP Armstrong, SJ Hill, KDG Pfleger
Frontiers in Endocrinology, 2014frontiersin.org
Guanine nucleotide binding protein (G protein)-coupled receptors (GPCRs) function in
complexes with a range of molecules and proteins including ligands, G proteins, arrestins,
ubiquitin, and other receptors. Elements of these complexes may interact constitutively or
dynamically, dependent upon factors such as ligand binding, phosphorylation, and
dephosphorylation. They may also be allosterically modulated by other proteins in a manner
that changes temporally and spatially within the cell. Elucidating how these complexes …
Guanine nucleotide binding protein (G protein)-coupled receptors (GPCRs) function in complexes with a range of molecules and proteins including ligands, G proteins, arrestins, ubiquitin, and other receptors. Elements of these complexes may interact constitutively or dynamically, dependent upon factors such as ligand binding, phosphorylation, and dephosphorylation. They may also be allosterically modulated by other proteins in a manner that changes temporally and spatially within the cell. Elucidating how these complexes function has been greatly enhanced by biophysical technologies that are able to monitor proximity and/or binding, often in real time and in live cells. These include resonance energy transfer approaches such as bioluminescence resonance energy transfer (BRET) and fluorescence resonance energy transfer (FRET). Furthermore, the use of fluorescent ligands has enabled novel insights into allosteric interactions between GPCRs. Consequently, biophysical approaches are helping to unlock the amazing diversity and bias in G protein-coupled receptor signaling.
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