ArticleThe Journal of biological chemistry2019
Structural architecture of a dimeric class C GPCR based on co-trafficking of sweet taste receptor subunits.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- Large serine recombinase-mediated gene insertion for high-throughput screens: advantages, design principles, and applications.Nucleic acids research · 2026Review
- Sweet Taste Receptor Genetic VariationNutrients · 2026Article
- Phenotypic pleiotropy of missense variants in human B cell confinement receptor P2RY8.Cell genomics · 2025Article
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- Article
- Steviol rebaudiosides bind to four different sites of the human sweet taste receptor (T1R2/T1R3) complex explaining confusing experiments.Communications chemistry · 2024Article
- Deep mutational scanning reveals sequence to function constraints for SWEET family transporters.bioRxiv : the preprint server for biology · 2024Article
- Molecular basis of proton-sensing by G protein-coupled receptors.bioRxiv : the preprint server for biology · 2024Article
- Novel gurmarin-like peptides from Gymnema sylvestre and their interactions with the sweet taste receptor T1R2/T1R3.Chemical senses · 2024Article
- Oligomerization of Monoamine Transporters.Sub-cellular biochemistry · 2024Review
- Sequence basis for selectivity of ephrin-B2 ligand for Eph receptors and pathogenic henipavirus G glycoproteins.Journal of virology · 2023Article
- Deep mutational scanning of proteins in mammalian cells.Cell reports methods · 2023Review
- Heterodimerization of Chemoreceptors TAS1R3 and mGluInternational journal of molecular sciences · 2023Article
- Deep mutagenesis scanning using whole trimeric SARS-CoV-2 spike highlights the importance of NTD-RBD interactions in determining spike phenotype.PLoS pathogens · 2023Article
- HLA-II immunopeptidome profiling and deep learning reveal features of antigenicity to inform antigen discovery.Immunity · 2023Article
- Prediction of dynamic allostery for the transmembrane domain of the sweet taste receptor subunit, TAS1R3.Communications biology · 2023Article
- Multiple mechanisms of self-association of chemokine receptors CXCR4 and CCR5 demonstrated by deep mutagenesis.bioRxiv : the preprint server for biology · 2023Article
- Xeno interactions between MHC-I proteins and molecular chaperones enable ligand exchange on a broad repertoire of HLA allotypes.Science advances · 2023Article
- Sweet taste receptor agonists attenuate macrophage IL-1β expression and eosinophilic inflammation linked to autophagy deficiency in myeloid cells.Clinical and translational medicine · 2022Article
- Recent Advances in Machine Learning Variant Effect Prediction Tools for Protein Engineering.Industrial & engineering chemistry research · 2022Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Class C G protein-coupled receptors (GPCRs) are obligatory dimers that are particularly important for neuronal responses to endogenous and environmental stimuli. Ligand recognition through large extracellular domains leads to the reorganization of transmembrane regions to activate G protein signaling. Although structures of individual domains are known, the complete architecture of a class C GPCR and the mechanism of interdomain coupling during receptor activation are unclear. By screening a mutagenesis library of the human class C sweet taste receptor subunit T1R2, we enhanced surface expression and identified a dibasic intracellular retention motif that modulates surface expression and co-trafficking with its heterodimeric partner T1R3. Using a highly expressed T1R2 variant, dimerization sites along the entire subunit within all the structural domains were identified by a comprehensive mutational scan for co-trafficking with T1R3 in human cells. The data further reveal that the C terminus of the extracellular cysteine-rich domain needs to be properly folded for T1R3 dimerization and co-trafficking, but not for surface expression of T1R2 alone. These results guided the modeling of the T1R2-T1R3 dimer in living cells, which predicts a twisted arrangement of domains around the central axis, and a continuous folded structure between transmembrane domain loops and the cysteine-rich domains. These insights have implications for how conformational changes between domains are coupled within class C GPCRs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.