ArticleProceedings of the National Academy of Sciences of the United States of America2020
Structural instability and divergence from conserved residues underlie intracellular retention of mammalian odorant receptors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 61 citations in OpenAlex.
- Allosteric Gating Mechanism Regulates Odorant Selectivity and Antagonism in Odorant Receptors.bioRxiv : the preprint server for biology · 2026Article
- Rapid odorant metabolism organizes identity- and timing-based odor representations by olfactory bulb inputs and outputs.bioRxiv : the preprint server for biology · 2026Article
- Structural basis of the sweat odorant HMHA recognition by the human odorant receptor OR52E8.Communications biology · 2026Article
- Elucidating odorant synergy in red wine: through olfactory receptor-based profiling.NPJ science of food · 2026Article
- Identifying Key Regulators in Odorant Receptor Trafficking.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Molecular Mechanism Analysis of the Activation of Human Olfactory Receptor OR9Q2 by 4-Methylphenol.Foods (Basel, Switzerland) · 2025Article
- Surface delivery quantification reveals distinct trafficking efficiencies among clustered protocadherin isoforms.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- An odorant receptor for a key odor constituent of ambergris.Communications biology · 2025Article
- Antagonists Enhance Cell-Surface Expression of Mammalian Odorant Receptors.International journal of molecular sciences · 2025Article
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- Conserved pattern-based classification of human odorant receptor multigene family.Scientific reports · 2024Article
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- Geosmin, a Food- and Water-Deteriorating Sesquiterpenoid and Ambivalent Semiochemical, Activates Evolutionary Conserved Receptor OR11A1.Journal of agricultural and food chemistry · 2024Article
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- Enhancement of transcription efficiency by TAR-Tat system increases the functional expression of human olfactory receptors.PloS one · 2024Article
- Deciphering olfactory receptor binding mechanisms: a structural and dynamic perspective on olfactory receptors.Frontiers in molecular biosciences · 2024Review
- Understanding the molecular mechanisms of odorant binding and activation of the human OR52 family.Nature communications · 2023Article
- Engineered odorant receptors illuminate structural principles of odor discrimination.bioRxiv : the preprint server for biology · 2023Article
- Human Olfactory Receptor Sensor for Odor Reconstitution.Sensors (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
Mammalian odorant receptors are a diverse and rapidly evolving set of G protein-coupled receptors expressed in olfactory cilia membranes. Most odorant receptors show little to no cell surface expression in nonolfactory cells due to endoplasmic reticulum retention, which has slowed down biochemical studies. Here we provide evidence that structural instability and divergence from conserved residues of individual odorant receptors underlie intracellular retention using a combination of large-scale screening of odorant receptors cell surface expression in heterologous cells, point mutations, structural modeling, and machine learning techniques. We demonstrate the importance of conserved residues by synthesizing consensus odorant receptors that show high levels of cell surface expression similar to conventional G protein-coupled receptors. Furthermore, we associate in silico structural instability with poor cell surface expression using molecular dynamics simulations. We propose an enhanced evolutionary capacitance of olfactory sensory neurons that enable the functional expression of odorant receptors with cryptic mutations.
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Registered trials
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.