By Tiina P. Iismaa Ph.D., Trevor J. Biden Ph.D., John Shine Ph.D. (auth.)
This e-book is ready the new advances within the structural and sensible characterization of receptors that effect intracellular signalling occasions via interplay with intracellular GTP-binding proteins (G proteins). Molecular cloning of individuals of the G protein-coupled receptor superfamily has complemented pharmacological investigations in delivering a awareness of the structural and sensible range of those receptors. An elevated knowing of the involvement of specific receptor subtypes in basic and pathophysiological procedures represents interesting probabilities for the advance of hugely particular and potent healing agents.
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Additional resources for G Protein-Coupled Receptors
However, if the sequential order of TM helices in bacteriorhodopsin is ignored, considerable homology is observed between TM helices III, VII and I of bacteriorhodopsin with TM helices 5, 3 and 7, respectively, of G protein-coupled receptors. This has led to the suggestion that exon shuffling may have occurred in evolution of the ancestral G protein-coupled receptor gene from the gene encoding bacteriorhodopsin. 110 An alternative hypothesis is based upon the observation of intragenic as well as intergenic similarities between helices 1-3 and 5-7 of bacteriorhodopsin and a number of adrenergic and muscarinic acetylcholine G protein-coupled receptors, leading to the suggestion that an ancestral gene may have evolved through a duplication event, with TM helices 5-7 originating as duplicates of helices 1-3.
5), and is also evident at the level of receptors interacting with the same ligand, both within and between species. This second cloning strategy has resulted in the rapid isolation of a large number of receptors and receptor subtypes, as a consequence of the extensive sequence homology now known to exist between members of the superfamily. It has allowed the identification of molecular subtypes for particular ligands which were not delineated by previous pharmacological characterizations of receptor populations.
Construction of a genomic DNA library from one such transformant afforded isolation of the human vasopressin V 2 receptor gene and its functional expression in stably transfected mouse cells provided the means for isolation of the eDNA encoding this human receptor. 217 Another method which takes advantage of elevation of intracellular cAMP levels by stimulation of adenylyl cyclase through activated receptors is based on transcriptional induction of a cAMP-responsive luciferase reporter gene. The eDNA encoding the rat PACAP type-I (PACAPR-2) receptor was cloned 23 using this procedure by expresswn of the appropriate reporter gene construct in porcine renal epithelial LLC PKl cells.