AI Article Synopsis
- The residue Arg3.50, found in class A GPCRs, plays a key role in stabilizing both the inactive and active states of these receptors, specifically influencing receptor-G protein interactions.
- Research indicates that the function of Arg3.50 can vary depending on the specific GPCR being studied.
- The authors conducted molecular-dynamics simulations on the dopamine D2 receptor to explore the dual role of Arg1323.50, showing it stabilizes the inactive form while also enhancing G protein coupling upon dopamine binding.
Article Abstract
Residue Arg3.50 belongs to the highly conserved DRY-motif of class A GPCRs, which is located at the bottom of TM3. On the one hand, Arg3.50 has been reported to help stabilize the inactive state of GPCRs, but on the other hand has also been shown to be crucial for stabilizing active receptor conformations and mediating receptor-G protein coupling. The combined results of these studies suggest that the exact function of Arg3.50 is likely to be receptor-dependent and must be characterized independently for every GPCR. Consequently, we now present comparative molecular-dynamics simulations that use our recently described inactive-state and Gα-bound active-state homology models of the dopamine D2 receptor (D2R), which are either bound to dopamine or ligand-free, performed to identify the function of Arg1323.50 in D2R. Our results are consistent with a dynamic model of D2R activation in which Arg1323.50 adopts a dual role, both by stabilizing the inactive-state receptor conformation and enhancing dopamine-dependent D2R-G protein coupling.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4704829 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0146612 | PLOS |
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