Coevolution underlies GPCR-G protein selectivity and functionality

Author:

Seo Min Jae,Heo Joongyu,Kim Kyunghui,Chung Ka Young,Yu Wookyung

Abstract

AbstractG 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.

Funder

Ministry of Science and ICT, South Korea

the Ministry of Science and ICT of Korea

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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