Universal Properties and Specificities of the beta(2)-Adrenergic Receptor-G(s) Protein Complex Activation Mechanism Revealed by All-Atom Molecular Dynamics Simulations

Mitra, Argha and Sarkar, Arijit and Borics, Attila (2021) Universal Properties and Specificities of the beta(2)-Adrenergic Receptor-G(s) Protein Complex Activation Mechanism Revealed by All-Atom Molecular Dynamics Simulations. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22 (19). ISSN 1661-6596

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Abstract

G protein-coupled receptors (GPCRs) are transmembrane proteins of high pharmacological relevance. It has been proposed that their activity is linked to structurally distinct, dynamically interconverting functional states and the process of activation relies on an interconnecting network of conformational switches in the transmembrane domain. However, it is yet to be uncovered how ligands with different extents of functional effect exert their actions. According to our recent hypothesis, based on indirect observations and the literature data, the transmission of the external stimulus to the intracellular surface is accompanied by the shift of macroscopic polarization in the transmembrane domain, furnished by concerted movements of highly conserved polar motifs and the rearrangement of polar species. In this follow-up study, we have examined the beta(2)-adrenergic receptor (beta(2)AR) to see if our hypothesis drawn from an extensive study of the mu-opioid receptor (MOP) is fundamental and directly transferable to other class A GPCRs. We have found that there are some general similarities between the two receptors, in agreement with previous studies, and there are some receptor-specific differences that could be associated with different signaling pathways.

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