Agonist induction, conformational selection, and mutant receptors

FEBS Letters

Giraldo, Jesús¹ 

[1] Grup de Modelització Estructural i Funcional de Sistemes Biològics, Institut de Neurociències and Unitat de Bioestadı́stica, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain

关键词: G protein-coupled receptor;    Agonist induction;    Conformational selection;    Signal transduction;    Mutant receptor;    Multiple state;   

DOI  :  10.1016/S0014-5793(03)01404-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Current models of receptor activation are based on either of two basic mechanisms: agonist induction or conformational selection. The importance of one pathway relative to the other is controversial. In this article, the impossibility of distinguishing between the two mechanisms under a thermodynamic approach is shown. The effect of receptor mutation on the constants governing ligand–receptor equilibria is discussed. The two-state model of agonism both in its original formulation (one cycle) and including multiple active states (multiple cycles) is used. Pharmacological equations for the double (two cycles) two-state model are derived. The simulations performed suggest that the double two-state model of agonism can be a useful model for assessing quantitatively the changes in pharmacological activity following receptor mutation.

【 授权许可】

Unknown