Structural Biology of Membrane Transporters and Channels

Membrane transporters and channels are amazing molecules in the cell. Our laboratory aims to understand their molecular mechanisms by structural, biochemical & biophysical approaches. Recently, we determined the structures of the formate channel FocA from Vibrio cholerae, without and with formate ions bound. The selectivity filter in FocA consists of a cytoplasmic slit and a central constriction ring. Interactions of the filter with formate ions provide a structural basis for the substrate selectivity of the channel. The structures also suggest a possible gating mechanism that movements of a cytosolic loop open and close the channel. This is the first time that the ion selectivity and gating mechanism is understood for an organic-ion channel.

In 2003, we solved the structure of the glycerol-3-phosphate transporter (GlpT) from the E. coli inner membrane. The protein is a member of the major facilitator superfamily (MFS), the large membrane transporter family with over 80,000 identified members. Together with the lactose permease structure, this is the first MSF structure ever determined to high resolution. The transporter structure suggests that the substrate translocation is by alternating-access via a rocker-switch mechanism.

MOVIE1 - GlpT structure
MOVIE2 - Proposed rocker-switch mechanism