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Coevolution underlies GPCR-G protein selectivity and functionality

Title
Coevolution underlies GPCR-G protein selectivity and functionality
Authors
Seo, Min JaeHeo, JoongyuKim, KyunghuiChung, Ka-youngYu, Wookyung
DGIST Authors
Seo, Min Jae; Heo, Joongyu; Kim, Kyunghui; Chung, Ka-young; Yu, Wookyung
Issue Date
2021-04
Citation
Scientific Reports, 11(1), 7858-154
Type
Article
Keywords
STRUCTURAL BASISCOUPLED RECEPTORSALPHA-SUBUNITMOLECULAR SWITCHESSEQUENCE ALIGNMENTAMINO-ACIDSDETERMINANTSACTIVATIONSPECIFICITYTARGETS
ISSN
2045-2322
Abstract
G protein-coupled receptors (GPCRs) regulate diverse physiological events, which makes them as the major targets for many approved drugs. G proteins are downstream molecules that receive signals from GPCRs and trigger cell responses. The GPCR-G protein selectivity mechanism on how they properly and timely interact is still unclear. Here, we analyzed model GPCRs (i.e. HTR, DAR) and Gα proteins with a coevolutionary tool, statistical coupling analysis. The results suggested that 5-hydroxytryptamine receptors and dopamine receptors have common conserved and coevolved residues. The Gα protein also have conserved and coevolved residues. These coevolved residues were implicated in the molecular functions of the analyzed proteins. We also found specific coevolving pairs related to the selectivity between GPCR and G protein were identified. We propose that these results would contribute to better understandings of not only the functional residues of GPCRs and Gα proteins but also GPCR-G protein selectivity mechanisms. © 2021, The Author(s).
URI
http://hdl.handle.net/20.500.11750/15330
DOI
10.1038/s41598-021-87251-6
Publisher
Nature Publishing Group
Related Researcher
  • Author Yu, Wookyung Laboratory of Protein Biophysics
  • Research Interests protein biophysics; protein folding; protein dynamics and conformational change
Files:
Collection:
Department of Brain SciencesLaboratory of Protein Biophysics1. Journal Articles


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