The allosteric landscape of a fundamental molecular switch
Molecular switch proteins whose cycling between states is controlled by opposing regulators are central to biological signal transduction. As switch proteins function within highly connected interaction networks, the fundamental question arises of how functional specificity is achieved when different processes share common regulators. We have focused on a paradigm molecular switch, the small GTPase Ran/Gsp1, which regulates diverse processes including nucleocytoplasmic transport, cell cycle progression, and RNA processing. Using systematic mutational perturbations of the switch, quantitative genetic interaction mapping, analysis of rewiring of physical interaction networks, in vitro biochemistry, and NMR, I will propose a model of how different biological processes are sensitive to different quantitative regimes of switch function. Our results highlight a considerable role of allostery in regulating the switch.