Jing Li and Emad Tajkhorshid.
Ion-releasing state of a secondary membrane transporter.
Biophysical Journal, 97:L29-L31, 2009.
LI2009-ET
Capturing the first inward-facing conformation of LeuT-fold substrate cation transporters,
the structure of a bacterial +-coupled galactose transporter (vSGLT) reports a
substrate-bound state, and provides an important opportunity for a better understanding
of the alternating-access mechanism in secondary transporters. In repeated 200ns
molecular dynamics simulations we find the substrate does not diffuse out from the
transporter, but shows significant fluctuation in specific period, in which a state where
substrate diffuses out from its binding pocket is captured. Steered molecular dynamics
(SMD) initiated from this point can pull out the substrate to cytoplasm without appreciable
energy barrier observed in other SMDs. The dynamics of substrate in equilibrium and SMD
simulations, verifies that the release of + not only precedes that of substrate, but also
facilitate it, and suggests that the substrate in this conformation of vSGLT can be released
to cytoplasm without significant conformational change, thus, cast light on key steps in
the cytoplasmic functional cycle of the LeuT-fold substrate cation transporters.
