FAR7 Antibody

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Description

Definition and Overview of FAR7 Antibody

The FAR7 antibody targets the FAR7 protein, a component of the Far3-7-8-9-10-11 (Far) complex in Saccharomyces cerevisiae. This complex localizes to the endoplasmic reticulum (ER) and plays a critical role in TORC2 signaling, which regulates cellular processes such as lipid biosynthesis, cell wall integrity, and stress response . FAR7 is part of a membrane-associated subcomplex (Far9/Far10/Far11) required for ER localization and stability of the Far complex .

Functional Role in TORC2 Signaling

FAR7 is essential for ER localization of the Far complex, which modulates TORC2 activity. Deletion of FAR7 disrupts:

  • Complex assembly: Loss of Far8-Far11 interaction .

  • TORC2 signaling: Impaired phosphorylation of downstream targets like Ypk1/2 kinases.

Experimental findings:

  • Deletion mutants (far7Δ) exhibit defective sphingolipid biosynthesis and cell wall stress responses .

  • Coimmunoprecipitation assays confirm FAR7’s role in bridging Far8 and Far9/Far10/Far11 (Fig. 6) .

Table 1: Yeast Strains and Phenotypes in Far Complex Studies

Strain GenotypeObserved Phenotype
far7ΔDisrupted Far8-Far11 interaction
far7Δ far3ΔLoss of core subcomplex stability
far7Δ far9ΔER mislocalization of Far complex

Table 2: Protein-Protein Interaction Network

Bait ProteinPrey Proteins Identified
Far9-mycFar7, Far8, Far10, Far11
Far7-mycFar3, Far8, Far9

Implications and Future Directions

FAR7’s role in TORC2 signaling highlights its potential as a therapeutic target for diseases linked to lipid metabolism or ER stress. Current research focuses on:

  • Mechanistic insights: How Far complex dynamics regulate TORC2 substrate specificity.

  • Translational applications: Engineering FAR7-specific antibodies for modulating ER-associated signaling pathways.

Product Specs

Buffer
**Preservative:** 0.03% Proclin 300
**Constituents:** 50% Glycerol, 0.01M PBS, pH 7.4
Form
Liquid
Lead Time
Made-to-order (14-16 weeks)
Synonyms
FAR7 antibody; At5g22420 antibody; MWD9.22Putative fatty acyl-CoA reductase 7 antibody
Target Names
FAR7
Uniprot No.

Q&A

FAQs for FAR7 Antibody Research

Advanced Research Questions

  • What strategies enhance FAR7 antibody effector functions (e.g., ADCC, ADCP) for therapeutic applications?

    • Fc engineering:

      • FcγR optimization: Introduce mutations (e.g., GRLR or GAALIE variants) to enhance binding to activating FcγRs (e.g., FcγRIIIa) while minimizing inhibitory FcγRIIb engagement .

      • Hexamerization: Mutations like T437R/K248E promote Fc–Fc interactions, improving receptor clustering .

    Fc ModificationFunctional OutcomeTherapeutic Impact
    GAALIE variant5x dose reduction in SARS-CoV-2 models Improved tumor regression in Claudin18.2 xenografts
    IgG2 isotype (h2B)Compact Fab conformationEnhanced CD40 agonism in T cells
  • How to validate FAR7 antibody specificity in complex biological matrices?

    • Integrated approaches:

      • Immunoprecipitation-MS: Confirm target protein enrichment and exclude off-target binding .

      • Multiclonal validation: Use a recombinant multiclonal antibody panel to detect multiple epitopes .

      • In vivo models: Generate transgenic mice expressing humanized FAR7 to assess toxicity and specificity .

Data Contradiction Analysis

  • Conflicting reports on FAR7 expression levels in tumor vs. normal tissues: How to reconcile?

    • Root cause analysis:

      • Antibody validation gaps: 30% of commercial antibodies fail in orthogonal assays (e.g., IHC vs. Western blot) .

      • Subtype specificity: FAR7 may be overexpressed only in mesenchymal/proliferative tumor subtypes (e.g., ovarian serous cystadenocarcinoma) .

    • Resolution workflow:

      1. Use RNA-seq data (e.g., TCGA) to correlate protein expression with transcriptional subtypes.

      2. Validate with KO cell lines and isotype controls in parallel assays .

Experimental Design for Therapeutic Development

  • How to optimize combination therapies using FAR7-targeted agents?

    • Synergy screening:

      • Checkpoint inhibitors: Co-administer with anti-PD-1, as seen in Claudin18.2 models (4A7 + anti-mPD-1 achieved 80% tumor regression) .

      • ADC payloads: Conjugate FAR7 antibodies to MMAE (e.g., F7-ADC induced tumor xenograft regression at 3 mg/kg) .

    CombinationMechanismOutcome
    FAR7-ADC + anti-PD-1Immune activation + cytotoxic payloadSuperior tumor growth inhibition vs. monotherapy
    Fc-engineered FAR7 + CAR-TEnhanced phagocytosis & T-cell recruitmentProposed for low-antigen-density tumors

Computational & Structural Insights

  • How to predict FAR7 antibody-antigen binding interfaces for rational engineering?

    • Tools:

      • Homology modeling: Use AbPredict or PIGS servers for Fv region modeling .

      • MD simulations: Refine docking predictions (e.g., STn-antibody interactions) .

    • Case study: Anti-Claudin18.2 antibodies were optimized using confocal microscopy-guided epitope mapping .

Methodological Recommendations

  • For in vivo studies: Use FcγR-humanized models to evaluate Fc-dependent effector functions .

  • For high-throughput screening: Employ autocrine surface-display systems to identify rare clones with optimal activity .

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