Modelling of the activation of G-protein coupled receptors: drug free constitutive receptor activity

Abstract

G-protein coupled receptors (GPCRs) form a crucial component of approximately 80% of hormone pathways. In this paper, the most popular mechanism for activation of GPCRs--the shuttling mechanism--is modelled mathematically. An asymptotic analysis of this model clarifies the dynamics of the system in the absence of drug, in particular which reactions dominate during the different timescales. Equilibrium analysis of the model demonstrates the model's ability to predict constitutive receptor activity.[PUBLICATION ABSTRACT]