Membrane protein folding, stability, and functions

Yu-Chu Chang

We investigate the biophysical and biochemical properties of membrane proteins, focusing on their folding, stability, and function. We use a variety of techniques, including novel methods to study membrane protein stability and biochemical assays to characterize the function of bacterial proteins involved in virulence.

Develop novel techniques to investigate membrane protein folding and stability

Our research investigates the biophysical and biochemical properties of helical membrane proteins, particularly their folding stability and kinetics. We develop new methods to study membrane protein stability in the lipid bilayer and lipid disc conditions.

Bacteriorhodopsin (bR) is used as the model membrane protein for us to develop different new methods. Steric trapping and clipped trapping techniques utilize the coupling of the folding of the target membrane protein to a binding event. The folding/unfolding event of the membrane protein can be driven by the binding of another soluble protein. These techniques aim to understand the folding properties of membrane protein in a more physiological lipid bilayer environment rather than denaturant-induced folding/unfolding conditions.

Study the virulence-related proteins of Salmonella

• Wzx: This integral membrane protein is involved in the lipopolysaccharide (LPS) biosynthesis process of gram-negative bacteria and serves as a lipid-linked oligosaccharide flippase in the pathway.
• YqiC: Through the protein-protein interaction studies, we found out YqiC’s function is tightly related to the energy protein in the bacteria, specifically in the electron transport chain (ETC).

Using combinatorial approaches, we explore these proteins' structural characteristics, functional mechanisms, and interaction networks. Since the knock-out strains of these genes significantly affect Salmonella's colonisation and invasion ability, they are potential drug targets for the future development of novel antibiotics.