GAL4-DBD-THRA-LBD-BSD

Background

Thyroid hormone receptor alpha (THRα, NR1A1), encoded by the THRA gene, is a ligand-activated nuclear receptor that mediates the actions of thyroid hormone, alongside the related THRβ subtype. THRα is highly expressed in the heart and other tissues involved in metabolic regulation, where it influences cardiac rhythm, development, growth, and energy metabolism. THRα binds thyroid hormone response elements in target gene promoters; in the absence of hormone it recruits corepressors, and binding of triiodothyronine (T3) triggers a conformational change that exchanges corepressors for coactivators to activate transcription. THRα is an important target in endocrine and metabolic research.

Product Description & Applications

This GAL4-DBD-THRA-LBD-BSD lentivirus expresses a chimeric protein in which the yeast GAL4 DNA-binding domain is fused to the ligand-binding domain (LBD) of human THRα. Upon ligand binding, the LBD changes conformation and recruits co-activators, and the chimera binds upstream GAL4 UAS elements to drive a fluorescent or luminescent reporter (GFP, RFP, or firefly luciferase). The GAL4-LBD design isolates LBD-mediated transactivation from endogenous nuclear receptor activity, giving high signal-to-noise and specificity for studying ligand interactions with THRα. The system is used to characterize THRα agonists, antagonists, and selective modulators in pharmacology and drug discovery, and is amenable to high-throughput screening by luminometry. Supplied as high-titer lentiviral particles that allow researchers to establish their own stable reporter cell lines, reducing repeated transfections.

About This Product

This lentiviral system expresses a chimeric protein consisting of the GAL4 DNA-binding domain fused to the ligand-binding domain (LBD) of THRA. Upon specific ligand binding, the LBD undergoes conformational change and recruits co-activators; the activated chimera binds upstream GAL4 response elements (UAS×5) to drive expression of a fluorescent or luminescent reporter (GFP, RFP, or Firefly Luciferase) with high signal-to-noise relative to endogenous nuclear receptor background.

The GAL4-LBD design isolates LBD-mediated transactivation from A/B domain-driven constitutive activity and prevents cross-reactivity with endogenous nuclear receptor targets, enabling highly specific pharmacological characterization of LBD agonists, antagonists, and selective receptor modulators (SARMs/SERMs/SPPARMs). This system is established for drug discovery in academic and industrial settings, and is amenable to high-throughput screening (HTS) formats using luminometry.