Recombinant Human Olfactory receptor 11G2 (OR11G2)
Description
Gene and Protein Structure
The human OR11G2 gene encodes the olfactory receptor 11G2 protein, which belongs to the olfactory receptor family 11 subfamily G member 2. It is also identified by the alternative designation OR14-34 in scientific literature . Like other olfactory receptors, OR11G2 is encoded by a single coding-exon gene, which is a distinctive characteristic of this receptor family . This genetic architecture facilitates efficient expression of the receptor protein in specialized olfactory sensory neurons.
OR11G2, as a member of the G-protein-coupled receptor (GPCR) superfamily, exhibits the characteristic seven-transmembrane domain structure that is common to many neurotransmitter and hormone receptors . This structural configuration is essential for the receptor's function in binding odorant molecules and initiating signal transduction cascades. The seven hydrophobic transmembrane regions anchor the receptor within the cell membrane of olfactory neurons, with intervening loops that contribute to ligand binding and G-protein interaction.
Recombinant Production Technology
Recombinant Human OR11G2 refers to the artificially produced form of the receptor protein using molecular biology techniques. While the search results do not provide specific details about recombinant production methods for OR11G2, the general approach typically involves:
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Isolating the OR11G2 gene sequence from human genetic material
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Cloning this sequence into expression vectors
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Introducing these vectors into host cells (commonly bacteria, yeast, or mammalian cell lines)
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Inducing expression of the recombinant protein
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Purifying the expressed protein using chromatography or other separation techniques
The recombinant production of olfactory receptors presents significant challenges due to their hydrophobic nature and the difficulty in maintaining their proper folding and functionality outside their native membrane environment. These challenges have historically limited the detailed structural and functional characterization of olfactory receptors compared to other GPCR family members.
Signaling Mechanism
OR11G2, like other olfactory receptors, functions through G protein-coupled signal transduction pathways. When an odorant molecule binds to the receptor, it induces a conformational change that activates associated G proteins . This activation initiates a signaling cascade that ultimately leads to the generation of action potentials in olfactory sensory neurons, transmitting the signal to the brain where it is perceived as a specific smell.
The receptor is involved in several key biological processes that are essential for olfactory function, including:
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Detection of chemical stimuli involved in sensory perception of smell
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G protein-coupled receptor signaling pathway activation
These processes collectively enable the conversion of chemical information from the environment into neuronal signals that can be interpreted by the brain's olfactory centers.
Ligand Specificity
The specificity of OR11G2 for particular odorant molecules is determined by the unique structural features of its binding pocket, which is formed by the arrangement of its transmembrane domains. While the search results do not provide specific information about the exact odorant molecules that activate OR11G2, the general principles of olfactory receptor function suggest that:
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Each olfactory receptor, including OR11G2, responds to a range of odorant molecules with varying affinities
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A single odorant molecule can activate multiple olfactory receptors
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The combination of activated receptors creates a unique pattern that the brain interprets as a specific smell
Research into decoding the functions of olfactory receptors from their primary sequence suggests that the specific amino acid composition and arrangement within OR11G2 would determine its ligand binding profile and functional properties .
Chromosomal Location and Organization
OR11G2 is located on chromosome 11 in humans, which is notable for containing numerous olfactory receptor genes. The organization of olfactory receptor genes in genomic clusters suggests their evolution through gene duplication events. The presence of OR11G2 on chromosome 11 places it within a context where structural genomic aberrations may have evolutionary significance .
Research has identified that chromosome 11 has undergone significant evolutionary changes, including "four distinct centromere repositioning events in Catarrhini" as referenced in the literature . This evolutionary history may have implications for the functional diversification of olfactory receptor genes, including OR11G2.
Evolutionary Conservation
Comparative genomics approaches have identified orthologous genes to human OR11G2 in other mammalian species, including rats (Or11g2) . This evolutionary conservation suggests the functional importance of this receptor across mammalian lineages. The rat ortholog, Or11g2, shares similar functional annotations, including involvement in:
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Detection of chemical stimulus in sensory perception of smell
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G protein-coupled receptor signaling pathway
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Sensory perception of smell
Table 1: Comparison of Known Functional Annotations Between Human OR11G2 and Rat Or11g2
This conservation of structure and function across species highlights the evolutionary importance of this receptor in mammalian olfactory systems.
Promoter Architecture and Gene Regulation
Studies on the promoter architecture of olfactory receptor genes provide insights into the regulation of OR11G2 expression. While specific information about OR11G2 promoter architecture is not provided in the search results, research on mouse olfactory receptor genes suggests complex regulatory mechanisms that ensure the expression of a single olfactory receptor gene in each olfactory sensory neuron .
Understanding the promoter architecture and regulatory mechanisms of OR11G2 is crucial for comprehending how this receptor is selectively expressed in specific olfactory sensory neurons, contributing to the combinatorial coding of olfactory information.
Biomedical Applications
Recombinant OR11G2 has potential applications in various biomedical fields, including:
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Development of biosensors for the detection of specific chemicals in environmental or clinical samples
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Screening of novel compounds for olfactory properties in fragrance and flavor industries
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Understanding olfactory dysfunction in certain neurological conditions
The production of functional recombinant olfactory receptors, including OR11G2, could enable high-throughput screening assays to identify novel ligands with potential therapeutic or industrial applications.
Future Research Directions
Several promising research directions could advance our understanding of OR11G2 and its applications:
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Comprehensive ligand screening to identify the specific odorant molecules that activate OR11G2
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Structural studies to determine the three-dimensional configuration of the receptor and its binding pocket
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Investigation of potential genetic variations in OR11G2 and their association with differences in olfactory perception
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Development of improved expression systems for the production of functional recombinant OR11G2
These research directions could significantly enhance our understanding of the molecular basis of olfaction and potentially lead to novel applications in biomedicine and biotechnology.
Product Specs
Note: We will prioritize shipping the format currently in stock. However, if you have a specific format requirement, please indicate it in your order notes. We will fulfill your request if possible.
Note: All our proteins are shipped with standard blue ice packs by default. If you require dry ice shipping, please inform us in advance. Additional fees may apply.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Target Background
Q&A
What is Olfactory Receptor 11G2 and what is its biological function?
Olfactory receptor 11G2 (OR11G2), also known as OR14-34, is a protein encoded by the OR11G2 gene in humans. It belongs to the large family of G-protein-coupled receptors (GPCRs) that arise from single coding-exon genes. OR11G2 functions as a chemosensor that interacts with odorant molecules in the nasal epithelium to initiate a neuronal response, ultimately triggering the perception of smell . Like other olfactory receptors, OR11G2 shares a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and participates in the G protein-mediated transduction of odorant signals . Recent research indicates that OR11G2 can recognize ethyl 3-phenylglycidate as an agonist, which not only activates the receptor but also enhances its expression levels in experimental systems .
What experimental methods are validated for detecting OR11G2?
Multiple experimental approaches have been validated for detecting OR11G2 in research settings:
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Western Blot (WB): Allows quantification of total OR11G2 protein expression using rabbit polyclonal antibodies at recommended dilutions of 1:500-1:2000 .
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Immunofluorescence (IF): Enables visualization of cellular localization of OR11G2 using validated antibodies at dilutions of 1:200-1:1000 .
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ELISA: Provides quantitative measurement of OR11G2 protein levels with high sensitivity at recommended dilutions of approximately 1:40000 .
When conducting these assays, researchers should use affinity-purified antibodies raised against the C-terminal region of human OR11G2 for optimal specificity and sensitivity .
What challenges are associated with OR11G2 expression systems?
Expression of OR11G2 and other human olfactory receptors in heterologous cell systems presents significant technical challenges:
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Structural instability: OR11G2 may exhibit conformational instability when expressed outside its native environment, leading to protein misfolding .
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Poor trafficking: The receptor often fails to properly traffic to the cell surface in heterologous expression systems .
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Low expression levels: Total protein expression is typically poor, complicating functional studies and protein purification efforts .
These challenges are not unique to OR11G2 but are common across the olfactory receptor family. Evidence suggests that divergence from consensus sequences and conserved residues contributes to the retention of olfactory receptors inside cells, possibly due to structural instability .
What strategies can improve the functional expression of OR11G2?
Researchers have developed several approaches to enhance the functional expression of OR11G2 and other olfactory receptors:
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Agonist-mediated enhancement: Treatment with ethyl 3-phenylglycidate, which acts as an agonist for OR11G2, has been shown to significantly increase both total and cell surface expression levels in a dose-dependent manner . This compound appears to stabilize the receptor by binding to its ligand-binding pocket.
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Structural stabilization: Introduction of specific mutations that enhance structural stability, particularly salt bridges, can improve surface expression levels. Studies with related olfactory receptors have demonstrated that engineered consensus ORs with inserted salt bridges show surface expression levels comparable to canonical GPCRs .
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Molecular chaperones: Co-expression with specialized chaperone proteins that are naturally present in olfactory sensory neurons can facilitate proper folding and trafficking.
The combined application of these approaches may yield synergistic benefits for achieving functional expression of OR11G2 in experimental systems.
How do specific residues affect OR11G2 stability and function?
Although specific data for OR11G2 is limited, research on related olfactory receptors provides valuable insights into how conserved residues affect stability and function:
Molecular dynamics (MD) simulations of olfactory receptors have revealed that specific residues at positions 4.53 and 5.47 (Ballesteros-Weinstein numbering) are critical for structural stability . Well-trafficked ORs show more stable structures in MD simulations, while poorly trafficked variants exhibit greater flexibility and structural instability when inserted into cell membrane models .
For OR11G2 research, this suggests that:
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Mutations affecting conserved residues in transmembrane domains should be carefully analyzed for their impact on receptor stability
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Restoration of consensus residues at key positions may improve the receptor's functional expression
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Computational modeling and MD simulations can provide valuable insights into the structural consequences of specific mutations
What experimental controls are essential when studying OR11G2 expression?
When designing experiments to study OR11G2 expression and function, the following controls are essential:
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Positive control: Include a well-expressed canonical GPCR (e.g., β2-adrenergic receptor) to validate your expression system and detection methods.
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Vector-only control: Cells transfected with empty vector to establish baseline and account for non-specific effects.
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Randomization of experimental order: Critical to prevent batch effects that can lead to spurious associations. Approximately 95% of genetic studies have major problems with experimental design, particularly failure to randomize experimental order with respect to phenotypes of interest .
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Batch controls: When combining multiple experiments, include controls to identify and correct for batch effects, as these can severely confound results and lead to spurious associations .
The importance of proper experimental design cannot be overstated. Poor randomization has been identified as a universal problem, even in studies from top research centers, and can render real associations indistinguishable from experimental artifacts .
How can molecular dynamics simulations inform OR11G2 research?
Molecular dynamics (MD) simulations provide valuable insights into OR11G2 structure and function:
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Structural stability assessment: MD simulations with OR11G2 models embedded in explicit lipid bilayers can identify regions of instability that may hinder functional expression. Stable receptors typically show convergence to equilibrated structures with low root mean square deviations (RMSDs) .
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Ligand binding prediction: Computational docking combined with MD simulations can predict potential ligands and binding modes for OR11G2, guiding experimental validation efforts.
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Rational mutation design: Based on instability patterns identified in MD simulations, specific mutations can be designed to enhance receptor stability and surface expression.
For optimal results, multiple independent MD simulations (e.g., six 500 ns runs) should be performed to ensure statistical reliability . Analysis of RMSD values across these simulations can quantitatively assess structural stability under different conditions.
What methodological approaches are recommended for studying OR11G2-ligand interactions?
To investigate OR11G2-ligand interactions, researchers should consider the following methodological approaches:
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Calcium imaging assays: Since OR11G2 activation triggers calcium influx through the canonical olfactory signal transduction pathway, calcium imaging provides a functional readout of receptor activation. This can be performed using fluorescent calcium indicators in cells expressing OR11G2.
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Dose-response studies: When testing potential ligands like ethyl 3-phenylglycidate, perform dose-response experiments to characterize the receptor's sensitivity and response profile .
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Combined expression-function studies: As demonstrated with ethyl 3-phenylglycidate, some compounds can both activate the receptor and enhance its expression . Experimental designs should account for this dual effect by:
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Measuring expression levels (surface and total) at different ligand concentrations
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Assessing functional responses with normalized expression levels
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Determining the temporal relationship between ligand exposure and enhanced expression
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Cross-reactivity testing: Test OR11G2 against a panel of structurally related compounds to establish specificity profiles and structure-activity relationships.
How should recombinant OR11G2 be stored and handled for optimal stability?
Recombinant Human Olfactory receptor 11G2 (OR11G2) requires careful handling and storage to maintain its structural integrity and function:
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Extended storage: For long-term preservation, store at -20°C or -80°C .
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Freeze-thaw cycles: Minimize repeated freeze-thaw cycles as they can lead to protein denaturation and loss of activity.
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Working solutions: When preparing working dilutions, use buffers that maintain protein stability, typically containing glycerol, BSA, and preservatives similar to the storage formulation (e.g., PBS containing 50% glycerol, 0.5% BSA, and 0.02% sodium azide) .
Proper storage and handling practices are particularly important for olfactory receptors like OR11G2 that exhibit inherent structural instability.
What are the recommended approaches for validating OR11G2 antibody specificity?
When using antibodies against OR11G2, validation of specificity is crucial due to the structural similarity within the olfactory receptor family:
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Positive controls: Use known OR11G2-expressing cells (e.g., MCF7 cells have been documented for Western blot validation) .
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Epitope validation: Confirm that the antibody recognizes the intended epitope, typically from the C-terminal region of human OR11G2 .
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Specificity tests:
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Peptide competition assays to confirm specificity for the immunizing peptide
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Testing in multiple OR11G2-expressing and non-expressing cell lines
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Validation across multiple detection methods (WB, IF, ELISA)
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Recommended dilutions: Follow validated dilution ranges for each application (WB: 1:500-1:2000, IF: 1:200-1:1000, ELISA: 1:40000) .
Thorough validation ensures reliable experimental results and minimizes the risk of cross-reactivity with other olfactory receptors.
How might the study of OR11G2 contribute to understanding evolutionary aspects of olfactory receptors?
OR11G2 research offers several avenues for investigating evolutionary aspects of olfactory receptors:
The olfactory receptor gene family is the largest in the genome, with nomenclature for human ORs being independent of other organisms . Studying the sequence divergence and structural consequences in OR11G2 can provide insights into how rapid functional evolution of ORs occurs.
Evidence suggests that enhanced evolutionary capacitance in olfactory sensory neurons with olfactory-specific chaperones may enable this rapid functional evolution . Investigating how divergence from conserved residues affects OR11G2 stability and function could illuminate the molecular mechanisms underlying this evolutionary process.
Comparative studies of OR11G2 with its orthologs across species, particularly examining how structural stability and expression efficiency relate to sequence conservation, would provide valuable evolutionary insights.
What emerging technologies may advance OR11G2 research?
Several emerging technologies hold promise for advancing OR11G2 research:
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Cryo-electron microscopy (cryo-EM): As this technology continues to improve for membrane proteins, it may soon enable direct structural determination of OR11G2, providing crucial insights into its ligand-binding pocket and activation mechanisms.
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Single-cell transcriptomics: This approach can reveal the expression patterns of OR11G2 in specific olfactory sensory neuron populations and how its expression correlates with other genes.
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Advanced computational methods: Improved computational approaches, including deep learning for protein structure prediction and molecular dynamics simulations with enhanced sampling techniques, will provide more accurate models of OR11G2 structure and dynamics.
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Nanobody technology: Development of nanobodies against OR11G2 could provide new tools for studying its structure, function, and cellular localization with higher specificity than conventional antibodies.
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Organoid models: Olfactory epithelium organoids may provide more physiologically relevant systems for studying OR11G2 function compared to heterologous expression systems.
Integration of these technologies promises to overcome current limitations in OR11G2 research and provide deeper insights into its biology.
