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A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
A hypothesis for GPCR activation
Jerzy Ciarkowski1, Magdalena Witt, Rafał Slusarz
1University of Gdańsk, Faculty of Chemistry, ul, Sobieskiego 18, 80-952, Gdańsk, Poland. jurek@chem.univ.gda.pl
Abstract:
Growing evidence that rhodopsin (RD) and related G protein-coupled receptors form functional dimers/oligomers, followed by direct proof (using atomic force microscopy) that in the retina disc membrane RD associates into a paracrystalline network of rows of dimers, need models of the RD-transducin (Gt) complex that would envision an optimal RD dimer/oligomer able to satisfy all well-documented interactions with Gt. Of the models proposed so far, only a few refer to RD dimers and only one of them proposes a complex of Gt with an RD oligomer (Filipek S, Krzyśko KA, Fotiadis D, Liang Y, Saperstein DA, Engel, A, Palczewski K Photochem Photobiol Sci 3: 628-638, 2004). This paper puts forward a hypothesis on another arrangement of RD monomers into the reported network of rows of dimers. Arguments for the compatibility of this set-up with interactions and activation of RD in the complex with Gt, in particular, with the well-documented movement of transmembrane helix 6 and cytosolic loop 3, which is vital for RD activation, are provided and discussed.
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