Agonist induction and conformational selection during activation of a G-protein-coupled receptor

被引:60
作者
Hunyady, L
Vauquelin, G
Vanderheyden, P
机构
[1] Semmelweis Univ, Fac Med, Dept Physiol, H-1444 Budapest, Hungary
[2] Univ Libre Brussels, Inst Mol Biol & Biotechnol, Dept Mol & Biochem Pharmacol, B-1640 Rhode St Genese, Belgium
关键词
D O I
10.1016/S0165-6147(02)00050-0
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Substitutions of Asn111 of the AT(1) angiotensin receptor and mutations of the corresponding amino acids in other G-protein-coupled receptors (GPCRs) cause constitutive receptor activation. Ligand binding and signalling of constitutively active mutant GPCRs are discussed and similarities and differences during the activation of amine and peptide GPCRs are identified. Studies using the AT(1) receptor suggest that conformational selection is not sufficient to explain the mechanism of receptor activation, and that agonist binding to the receptor provides energy to induce activation of the receptor. Because agonist binding also actively facilitates the conformational rearrangements leading to activation of other GPCRs we propose that agonist induction should be considered as a general mechanism of GPCR activation.
引用
收藏
页码:81 / 86
页数:6
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