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Role of palmitoylation of cysteine 415 in functional coupling CB 1 receptor to Gα i2 protein
Author(s) -
Oddi Sergio,
Totaro Antonio,
Scipioni Lucia,
Dufrusine Beatrice,
Stepniewski Tomasz Maciej,
Selent Jana,
Maccarrone Mauro,
Dainese Enrico
Publication year - 2017
Publication title -
biotechnology and applied biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 70
eISSN - 1470-8744
pISSN - 0885-4513
DOI - 10.1002/bab.1575
Subject(s) - palmitoylation , agonist , receptor , g protein coupled receptor , chemistry , partial agonist , cysteine , g protein , enzyme linked receptor , microbiology and biotechnology , biochemistry , 5 ht5a receptor , biophysics , biology , enzyme
In this study, we investigated the role of CB 1 palmitoylation in modulating the functional interaction with G proteins both in the absence and presence of agonist binding. Our data show that the nonpalmitoylated CB 1 receptor significantly reduced its association with Gα i2 . The agonist stimulation induced a partial dissociation of Gα i2 proteins from the wild‐type receptor, while on the C415A mutant the agonist binding was not able to induce a significant dissociation of Gα i2 from the receptor. The lack of palmitoyl chain seems to hamper the ability of the receptor to functionally interact with the Gα i2 and indicate that the palmitoyl chain is responsible for the functional transmission of the agonist‐induced conformational change in the receptor of the G protein. These data were further corroborated by molecular dynamics simulations. Overall these results suggest that palmitoylation of the CB 1 receptor finely tunes its interaction with G proteins and serves as a targeting signal for its functional regulation. Of note, the possibility to reversibly modulate the palmitoylation of CB 1 receptor may offer a coordinated process of regulation and could open new therapeutic approaches.