Steven(Yuhang) Wang


Graduate student

Beckman Institute, room 3041
405 N. Mathews Ave.
Urbana, IL 61801

Research projects

BetP | Betaine membrane transporter

Sodium coupled betaine transporter BetP is a representative member of the Betaine/Carnitine/Choline transporter (BCCT) family, which is from bacteria Corynebacterium glutamicum. Its major function is to accumulate osmolytes in order to prevent cell death in response to osmotic stress, which is a common challenge for soild bacteria.

BetP can transport one betaine (osmolyte) and symport two sodium ions, against the gradient of betaine across the membrane. This energy source is the high concentration of sodium ions outside the bacteria cell.

A recent study has shown that, with a single mutation G153D, BetP is able to transport a new subtrate (choline) under the gradient of pH across the membrane (Perez, EMBO, 2011). A crystal structure of the inward open state BetP-G153D (for simplicity, it will be denoted as BetP latter on) has been resolved by the same research group. However, how this BetP mutant transport choline with pH gradient is not yet known due to the low resolution (3.35 angstrom). Here a detailed study of the pH coupled subtrate release process in BetP G153D mutant is presented using molecular dynamics simulations.

Substrate(choline) release may follows a diagonal direction.

The substrate release is relatively fast when 153D is protonated (neutral state), which is within 100 ns. The same process takes much longer time when 153D is deprotonated (charged state). The estimated time scale is at least on the order of milliseconds.
Factors contributing to substrate release (1). Phe384 (located right at the center of the exit channel) Surpassing Phe384 is accompanied by the rotation of the pi-ring When 153D is at charged state, the attractive force between 153D and the substrate increases the energy cost the release process. (2). diameter of the substrate release channel. As discussed in a recent paper (Perez, et. al. Nature. 2012), transmembrane helices TM1' and TM5' act like the intracellular gate whose orientation anlge directly control the openness of the subtrate exit pathways.