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A Scalable, Multiplexed Assay for Decoding GPCR-Ligand Interactions with RNA Sequencing. | LitMetric

A Scalable, Multiplexed Assay for Decoding GPCR-Ligand Interactions with RNA Sequencing.

Cell Syst

Department of Chemistry and Biochemistry, UCLA-, DOE Institute for Genomics and Proteomics, Molecular Biology Institute, Quantitative and Computational Biology Institute, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, and Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA. Electronic address:

Published: March 2019

AI Article Synopsis

  • G protein-coupled receptors (GPCRs) help our cells detect and respond to different chemicals, with olfactory receptors (ORs) being the biggest group that helps us smell things.
  • Scientists created a new way to test lots of different chemicals on these receptors using special tools to see how they react.
  • They found 79 new connections between ORs and smells, even discovering new smells for 15 receptors that didn’t have any known connections before!

Article Abstract

G protein-coupled receptors (GPCRs) are central to how mammalian cells sense and respond to chemicals. Mammalian olfactory receptors (ORs), the largest family of GPCRs, mediate the sense of smell through activation by small molecules, though for most bonafide ligands, they have not been identified. Here, we introduce a platform to screen large chemical panels against multiplexed GPCR libraries using next-generation sequencing of barcoded genetic reporters in stably engineered human cell lines. We mapped 39 mammalian ORs against 181 odorants and identified 79 interactions that have not been reported to our knowledge, including ligands for 15 previously orphaned receptors. This multiplexed receptor assay allows the cost-effective mapping of large chemical libraries to receptor repertoires at scale.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6907015PMC
http://dx.doi.org/10.1016/j.cels.2019.02.009DOI Listing

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