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Development of biosensor for real-time detection of the G-protein molecular switch

Biosensor for real-time detection of the G-protein molecular switch
Credit: Nature Communications (2023). DOI: 10.1038/s41467-023-36911-4

A research team led by Professor Byung-Chang Suh has investigated the real-time effect of the G-protein cycle, which acts as a switch in the body, on the structural changes in G protein-coupled receptors (GPCRs). Their study is published in the journal Nature Communications.

GPCRs are activated by external signals such as , light, temperature, neurotransmitters, and hormones and are involved in numerous biological activities to the extent that nearly half of known drugs target GPCRs. GPCRs regulate various intracellular signaling pathways utilizing G proteins; however, the role of the reversible activation-deactivation cycle of the G protein on the structural changes in GPCRs has not yet been identified.

Professor Byung-Chang Suh's research team developed a new biosensor based on a utilizing human M3 muscarinic acetylcholine receptor (hM3R), a type of GPCR. Using this biosensor, they found that a GPCR-based single receptor sensor exhibited consecutive structural conversion via the G protein cycle.

The research team also showed that G-protein activation caused a two-step change of the hM3R structure, comprising a fast step of Gq protein binding and a subsequent slow step of the physical separation of the Gαq and Gβγ subunits.

They also found that the separated active Gαq formed a stable complex with ligand-activated hM3R and PLCβ, a downstream signaling pathway of Gαq.

In addition, applied research by Professor Suh's research team on the pathology of G protein-related gene mutations that cause , for example, and on the pharmacology of related therapeutic drug candidates found that Gβγ subunits separated from Gαq can independently bind to hM3R, providing clues to a possible treatment of related diseases.

Professor Suh, the corresponding author, said of this study, "We confirmed the real-time communication between active GPCRs and G proteins, which had been considered separate up to this point," and that they "expect it to be of great help to future molecular and individual-level research on diseases related to GPCRs and G protein and their treatments."

More information: Yong-Seok Kim et al, Two-step structural changes in M3 muscarinic receptor activation rely on the coupled Gq protein cycle, Nature Communications (2023). DOI: 10.1038/s41467-023-36911-4

Journal information: Nature Communications

Provided by Daegu Gyeongbuk Institute of Science and Technology

Citation: Development of biosensor for real-time detection of the G-protein molecular switch (2023, March 31) retrieved 13 July 2024 from
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