Molecular Dynamics Simulations of the Allosteric Modulation of the Adenosine A2a Receptor by a Mini-G Protein

Through their coupling to G proteins, G Protein-Coupled Receptors (GPCRs) trigger cellular responses to various signals. Some recent experiments have interestingly demonstrated that the G protein can also act on the receptor by favoring a closed conformation of its orthosteric site, even in the absence of a bound agonist. In this work, we explored such an allosteric modulation by performing extensive molecular dynamics simulations on the adenosine A2 receptor (A2aR) coupled to the Mini-Gs protein. In the presence of the Mini-Gs, we confirmed a restriction of the receptor’s agonist binding site that can be explained by a modulation of the intrinsic network of contacts of the receptor. Of interest, we observed similar effects with the C-terminal helix of the Mini-Gs, showing that the observed effect on the binding pocket results from direct local contacts with the bound protein partner that cause a rewiring of the whole receptor’s interaction network.

• Publication year

  2019

• Venue

  Scientific Reports

• Publication date

  2019-04-02

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1038/s41598-019-41980-xPMID 30940903PMCID 6445292
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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