Fig. 6: Five-state transport model of vSGLT.
a A unifying model of a five-state transport cycle for vSGLT based on an aggregate of data5,7,13,31,50 now including the effect of transmembrane potential. Outward-facing vSGLT (state 1) binds Na+ and undergoes a minor conformational change (state 2). Next, galactose binds and forms an occluded conformation (state 3). vSGLT then transitions to an inward conformation (state 4) where Na+ and galactose are stochastically released on the intracellular side (state 5). The inherent transmembrane potential (TMP) drives the conformation of vSGLT back to the outward-facing state where it is primed for another transport cycle. b Average transporter turnover rate as a function of voltage in a mixed-population of vSGLT with (Qgc = −0.7e, blue) and without (Qgc=0e, red) gating charge. c Steady state probability of inward-facing conformation (sum of states 4 and 5) as a function of voltage for mixed-population of transporters (blue curve), transporters in the inverted conformation (yellow), and transporters in the correct orientation (red) with a gating-charge of Qgc = −0.7e. d Single transporter rate of correctly oriented vSGLT with gating-charges of Qgc = −0.7e (blue), 0e (red), and +0.7e (yellow). All calculations in panels b-d use parameters from Supplementary Tables 4, 5 and Na+ and galactose concentrations employed from uptake assays.
