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A Putative α‐helical Gβγ‐coupling Domain in the Second Intracellular Loop of the 5‐HT 1A Receptor a
Author(s) -
ALBERT P. R.,
MORRIS S. J.,
GHAHREMANI M. H.,
STORRING J. M.,
LEMBO P. M. C.
Publication year - 1998
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1998.tb10186.x
Subject(s) - receptor , g protein coupled receptor , helix (gastropod) , biophysics , mutagenesis , coupling (piping) , chemistry , intracellular , g protein , cys loop receptors , stereochemistry , mutation , biochemistry , biology , acetylcholine receptor , materials science , nicotinic acetylcholine receptor , ecology , snail , gene , metallurgy
We have identified a conserved threonine residue in the second intracellular (i2) loop of the 5‐HT 1A receptor that when mutated to alanine prevents coupling to Gβγ‐mediated signaling, while preserving Gαi‐induced actions. 48 In this review, we investigate the characteristics and potential role of the i2 domain in the coupling of the 5‐HT 1A receptor and other receptors to G proteins. The i2 domain, as well as portions of the i3 domain, is predicted to form an amphipathic α‐helix with a positively charged face and a hydrophobic face. Mutagenesis experiments support a model in which the hydrophobic faces of these α‐helical domains form an intracellular binding “pocket” for interaction with G proteins. Embedded in the hydrophobic face, Thr149 is crucial for signaling through Gβγ subunits, perhaps via interaction with its hydroxyl side‐chain. Mutation of other residues of the i2 domain of Gi‐coupled receptors is required to substantiate the importance of the α‐helical i2 domain in receptor‐Gβγ signaling. If confirmed in other receptors, these results support a general model in which activated receptor and Gβγ subunits remain associated to interact with effectors in a receptor‐specific manner.