Recombinant Human Olfactory receptor 1A1 (OR1A1)
Description
Recombinant Expression Systems
OR1A1 has been expressed in two primary systems:
HEK293S Cell Line
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Method: Tetracycline-inducible stable expression with epitope tags .
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Functional Assays: Real-time cAMP measurements confirm receptor activity .
Transgenic Mouse Models
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Advantages:
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Example: 9x21-OR1A1-GCaMP6f mice show robust responses to ligands like MND (EC₅₀ = 388 nM) .
Ligand Binding Profile
OR1A1 is broadly tuned, responding to citrus/fruity odorants with varying affinities:
Functional and Mechanistic Insights
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Signaling Pathway: OR1A1 activates cAMP-mediated transduction upon ligand binding .
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Stereoselectivity: Distinguishes between enantiomers like (–)-carvone and (+)-carvone .
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Ligand Interactions:
Research Applications and Challenges
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Structural Biology: Purified OR1A1 enables crystallographic and NMR studies to resolve activation mechanisms .
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Drug Discovery: Serves as a model for olfactory GPCR pharmacology due to its broad ligand spectrum .
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Limitations: Poor plasma membrane expression in heterologous systems complicates high-throughput screening .
Future Directions
Product Specs
Please note: If you have specific requirements for the glycerol content, kindly specify them in your order remarks.
For lyophilized powder delivery forms, the buffer used prior to lyophilization is Tris/PBS-based buffer with 6% Trehalose.
Note: We prioritize shipping the format currently in stock. However, if you have a specific preference for the format, please indicate it in your order remarks. We will prepare the product according to your request.
Generally, the shelf life of the liquid form is 6 months at -20°C/-80°C. The shelf life of the lyophilized form is 12 months at -20°C/-80°C.
Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
Target Background
- Molecular mechanism of activation of human musk receptors OR5AN1 and OR1A1 by (R)-muscone and diverse other musk-smelling compounds. PMID: 29632183
- OR1A1 activation suppresses hepatic triglyceride metabolism by modulating HES-1, PPARG, and mtGPAT expression. PMID: 25817041
- Evolutionary conserved amino acid residues necessary for specific responsiveness of OR1A1 to odorants were identified. PMID: 17601748
Q&A
Basic Research Questions
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What is Human Olfactory Receptor 1A1 (OR1A1) and what is its primary function in olfaction?
Human Olfactory Receptor 1A1 (OR1A1) is a member of the G protein-coupled receptor (GPCR) superfamily and represents one of approximately 400 intact olfactory receptors in humans. It functions primarily as a chemosensor in the olfactory epithelium where it detects specific odorant molecules.
OR1A1 is notable for its ability to respond to nitromusks and certain other odorants. Unlike some olfactory receptors that respond to both macrocyclic and nitromusk compounds (such as OR5AN1), OR1A1 demonstrates relatively narrower musk-related ligand tuning, responding prominently to selected nitromusks like musk ambrette and to a lesser degree to other nitromusks, but not to macrocyclic or polycyclic musks .
Beyond olfaction, OR1A1 has been detected in multiple non-olfactory tissues, suggesting additional physiological roles outside of smell perception .
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What structural characteristics define OR1A1?
OR1A1 shares the characteristic seven-transmembrane α-helical structure common to G protein-coupled receptors. While the actual three-dimensional structure of OR1A1 has not yet been determined through crystallography, computational homology models have been developed based on other GPCRs.
Key structural features of OR1A1 include:
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Seven-transmembrane α-helical domains (TM1-TM7)
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An odorant binding pocket formed primarily by helices 3, 5, 6, and 7
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Critical binding residues including Tyr258 and Tyr251 in transmembrane α-helix 6 (TM6), Ile205 and Phe206 in transmembrane α-helix 5 (TM5), and Ile105 and Tyr113 in transmembrane α-helix 3 (TM3), and Leu184 in extracellular loop 2
Homology modeling studies have shown that the binding site of OR1A1 is located near the extracellular loop (ECL2) of the receptor, which differs from the deep binding site proposed for smaller odorants in other olfactory receptors .
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What are the confirmed ligands for OR1A1 and their relative binding affinities?
OR1A1 has been shown to respond to several odorants with varying affinities:
Ligand Relative Response Binding Properties Musk ambrette High Forms hydrogen bonds with Tyr258; EC50 in micromolar range Musk tibetene Moderate Forms hydrogen bonds with Tyr258 Musk xylene Low Weaker binding compared to other nitromusks Dihydrojasmone High Primary cognate odorant; affinity in micromolar range (-)-Carvone Moderate ~3.5× lower response than dihydrojasmone (+)-Carvone Low ~6.1× lower response than (-)-carvone 3-methyl-2,4-nonanedione (MND) Very High Best ligand for OR1A1; EC50 ~388 nM in optimized expression systems The stereoselective response to carvone isomers indicates the importance of three-dimensional structure in ligand recognition .
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How is OR1A1 signaling transduced within cells?
OR1A1 primarily signals through the canonical G protein-coupled pathway in olfactory sensory neurons:
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Upon odorant binding, OR1A1 couples to the olfactory G protein alpha subunit (Gαolf)
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Activated Gαolf stimulates adenylyl cyclase type 3 (Adcy3/AC3)
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This increases intracellular cyclic adenosine monophosphate (cAMP) levels
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Elevated cAMP opens cyclic nucleotide-gated (CNG) channels, causing membrane depolarization
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This triggers action potentials that are transmitted to the brain
In non-olfactory tissues, OR1A1 can activate alternative signaling pathways. For example, in hepatocytes, activation of the mouse homolog of OR1A1 (olfr43) stimulates the CREB-HES1-PPAR-γ signaling axis .
The signaling components (Gαolf, Adcy3, etc.) are primarily localized to the cilia of olfactory neurons, making this compartment sufficient for converting odorant binding to cAMP production in isolated preparations .
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