A combined activation mechanism for the glucagon receptor.
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ABSTRACT:
SUBMITTER: Mattedi G
PROVIDER: S-EPMC7355025 | biostudies-literature | 2020 Jul
REPOSITORIES: biostudies-literature
Publications
A combined activation mechanism for the glucagon receptor.
Mattedi Giulio G Acosta-Gutiérrez Silvia S Clark Timothy T Gervasio Francesco Luigi FL
Proceedings of the National Academy of Sciences of the United States of America 20200622 27
We report on a combined activation mechanism for a class B G-protein-coupled receptor (GPCR), the glucagon receptor. By computing the conformational free-energy landscape associated with the activation of the receptor-agonist complex and comparing it with that obtained with the ternary complex (receptor-agonist-G protein) we show that the agonist stabilizes the receptor in a preactivated complex, which is then fully activated upon binding of the G protein. The proposed mechanism contrasts with t ...[more]
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