{"id":7095,"date":"2025-12-09T16:18:00","date_gmt":"2025-12-09T16:18:00","guid":{"rendered":"https:\/\/www.sygnaturediscovery.com\/?post_type=case-study&p=7095"},"modified":"2026-02-02T18:00:13","modified_gmt":"2026-02-02T18:00:13","slug":"gpcr-assay-optimization-with-chimeric-g-proteins","status":"publish","type":"case-study","link":"https:\/\/www.sygnaturediscovery.com\/fr\/case-study\/gpcr-assay-optimization-with-chimeric-g-proteins\/","title":{"rendered":"GPCR Assay Optimization with Chimeric G Proteins"},"content":{"rendered":"\n

GPCR assay optimization using chimeric G proteins enables improved signalling control and enhanced assay performance. At Sygnature Discovery, we engineer custom G protein constructs to redirect signalling through preferred pathways, increasing assay sensitivity and streamlining functional readouts across diverse GPCR targets.\u00a0<\/h2>\n\n\n\n

Introduction<\/h3>\n\n\n\n

Cell-based assays represent an important step in \u00a0understanding the functional effects of GPCR \u00a0modulation. Having access to high quality cellular tools is critical in driving forward these studies, providing reproducible data and clear insight when you need it most. \u00a0One of the major challenges faced when developing robust functional GPCR assays is defining the \u00a0optimal signalling components to ensure a reliable downstream assay and lead optimization. While some GPCRs signal amicably via endogenous host cell G proteins, other receptros benefit from \u00a0over-expression of a specific G protein to enable coupling and downstream signalling. Additionally, when developing assay systems for orphan receptors lack of information on the target\u2019s signalling \u00a0mechanism can present a barrier to assay development and receptor de-orphanization.<\/p>\n\n\n\n

This collaboration underscores the multifunctional nature of GDF15-GFRAL-RET, impacting pathways critical for cellular stress response and energy balance. Given its regulatory influence across broad physiological systems, this pathway presents new therapeutic opportunities, particularly in areas such as metabolic disorders and cancer.<\/p>\n\n\n

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\n G Protein\n <\/div>\n <\/th>\n
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\n Characteristics\n <\/div>\n <\/th>\n
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\n Assay Readout\n <\/div>\n <\/th>\n <\/tr>\n <\/thead>\n \n
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SB-Gq\u03b115<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

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Wild-type SB-Gq\u03b115<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

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Calcium\/ IP1 assays<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n <\/tr>\n

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SB-Gq\/s<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

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Gq\u03b115 with c terminus optimized for Gs coupling<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

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Calcium\/ IP1 assays<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n <\/tr>\n

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SB-Gq\/i<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

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Gq\u03b115 with c terminus optimized for Gi coupling<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

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Calcium\/ IP1 assays<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n <\/tr>\n

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SB-Gq\/i (short)\t<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

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Gq\u03b115 with c terminus optimized for Gi coupling<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

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Calcium\/ IP1 assays<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n <\/tr>\n

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SB-Gq\u03b112<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

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Gq\u03b115 with c terminus optimized for G\u03b112 coupling<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

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Calcium\/ IP1 assays<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n <\/tr>\n

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SB-Gq\u03b113<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

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Gq\u03b115 with c terminus optimized for G\u03b113 coupling\t<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

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Calcium\/ IP1 assays<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n <\/tr>\n

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SB-Gs<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

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Wild-type Gs<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

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cAMP signalling assays<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n <\/tr>\n

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SB-Gs\/q<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

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Gs with c terminus optimized for Gq coupling<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

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cAMP signalling assays<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n <\/tr>\n

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SB-Gs\/i Gs<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

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Gs with c terminus optimized for Gi coupling<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

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cAMP signalling assays<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n <\/tr>\n

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SB-Gs\/\u03b112<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

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Gs with c terminus optimized for G \u03b112 coupling<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

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cAMP signalling assays<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n <\/tr>\n

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SB-Gs\/\u03b113<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

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Gs with c terminus optimized for G \u03b113 coupling<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

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cAMP signalling assays<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n <\/tr>\n <\/tbody>\n\n <\/table>\n <\/div>\n<\/div>\n\n<\/div>\n\t\t\n\t <\/section>\n\n\n\n

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Optimizing G Protein Coupling<\/h3>\n\n\n\n

Using a comprehensive panel of G protein constructs Sygnature Discovery\u2019s assay development team quickly iden\u00adtifyies optimal G proteins partners for your GPCR target, delivering robust functional assays for downstream drug discovery screening.<\/p>\n\n\n\n

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<\/a>GIF<\/span>\"\"<\/div>\"\"