Measuring the equilibrium dimerization of a polytopic membrane protein in lipid bilayers forms the basis of a new system for studying the physical forces that stabilize membrane protein association in membranes.
The G protein subunits Gβγ and the signaling lipid PIP2 are simultaneously needed to activate the potassium ion channel GIRK2 to control the voltage across a lipid bilayer, while sodium ions modulate these molecules' effects.
Single molecule microscopy combined with biochemical analyses show that a two-step lipid-binding mechanism of the SRP receptor balances the trade-off between speed and specificity during co-translational protein targeting.
The GIRK1 subunit contains a defective Na+-binding site but behaves as if it is permanently bound to a sodium ion, and therefore increases the affinity of Gβγ to GIRK1/4 hetero-tetrameric channels in lipid membranes.
Determining how GIRK2 activity depends on the concentration of Gβγ subunits in lipid membranes at different Na+ concentrations has allowed the Gβγ concentration generated during GABAB activation in neurons to be estimated.