Key result
Substitution of Asn111 and Asn295 in the AT1 receptor caused constitutive activation and altered ligand binding, indicating these residues control the active conformation of the receptor.
Population
Human embryonic kidney 293 cells expressing angiotensin AT1 receptors
Comparison
Site-directed mutagenesis of Asn111 and Asn295 vs Wild type AT1 receptors
Design
Preclinical
Authors
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AT1 receptor insights remain preclinical; leaves open whether Asn111/Asn295 modulation translates to human cardiovascular therapies.
The conformational change responsible for AT1 receptor activation depends on the interaction between Asn111 and Asn295 on transmembrane helices III and VII.
Balmforth et al. (1997) studied Angiotensin AT1 receptor activation. Site-directed mutagenesis (Asn111 and Asn295 substitution) vs. Wild type AT1 receptor was evaluated on Ligand binding affinity and basal generation of inositol trisphosphate. Substitution of Asn111 and Asn295 in the AT1 receptor caused constitutive activation and altered ligand binding, indicating these residues control the active conformation of the receptor.
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