Kinetic model of GPCR-G protein interactions reveals allokairic modulation of signaling

Abstract

Established models of ternary complex formation between hormone, G protein coupled receptor (GPCR), and G protein assume that all interactions occur under equilibrium conditions. However, several recent studies repeatedly demonstrate that the lifetime of events in ternary complex formation are comparable to the duration of hormone activated GPCR signaling. To understand the dynamics for such non-equilibrium conditions, we derive a transient kinetic model, wherein the receptor undergoes rate-limiting, G protein-catalyzed transitions between at least two hormone-bound active states.