Microsecond Molecular Dynamics Simulations Provide Insight into the Allosteric Mechanism of the Gs Protein Uncoupling from the beta(2) Adrenergic Receptor
2014 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 118, no 51, 14737-14744 p.Article in journal (Refereed) Published
Experiments have revealed that in the beta(2) adrenergic receptor (beta(2)AR)-Gs protein complex the a subunit (G alpha s) of the Gs protein can adopt either an open conformation or a closed conformation. In the open conformation the Gs protein prefers to bind to the beta(2)AR, while in the closed conformation an uncoupling of the Gs protein from the beta(2)AR occurs. However, the mechanism that leads to such different behaviors of the Gs protein remains unclear. Here, we report results from microsecond molecular dynamics simulations and community network analysis of the beta(2)AR-Gs complex with G alpha s in the open and closed conformations. We observed that the complex is stabilized differently in the open and closed conformations. The community network analysis reveals that in the closed conformation there exists strong allosteric communication between the beta(2)AR and G beta gamma, mediated by G alpha s. We suggest that such high information flows are necessary for the Gs protein uncoupling from the beta(2)AR.
Place, publisher, year, edition, pages
2014. Vol. 118, no 51, 14737-14744 p.
Coupled Receptors, Crystal-Structure, Structural Basis, Activation Mechanism, Nobel Lecture, Networks, Complex, Mode, Agonists
IdentifiersURN: urn:nbn:se:kth:diva-159623DOI: 10.1021/jp506579aISI: 000347360100002ScopusID: 2-s2.0-84919933719OAI: oai:DiVA.org:kth-159623DiVA: diva2:787157
FunderSwedish National Infrastructure for Computing (SNIC), SNIC025/12-38
QC 201502092015-02-092015-02-052015-05-20Bibliographically approved