Dissecting the mechanism of proton and cation conductance in viroporins using vibrational spectroscopy
In this project, we will use infrared spectroscopic methods to provide insight into the mechanisms of proton and cation conductance of the viroporins of the mosquito-borne Dengue 1 and the West Nile viruses. We will identify key amino acid residues that may be responsible for pH sensing or gating as well as monitor changes in structure and electrostatics of the channel interior, the latter using vibrational Stark effect probes, associated with the pore opening process. Finally, we will test the influence of viroporin inhibitors on the conductance mechanism and evaluate potential antiviral-resistance conferring mutations.
Baserga F, Dragelj J, Kozuch J, Mohrmann H, Knapp E-W, Stripp ST and Heberle J. (2021) Quantification of Local Electric Field Changes at the Active Site of Cytochrome c Oxidase by Fourier Transform Infrared Spectroelectrochemical TitrationsFront. Chem. 9:669452 (2021); doi: 10.3389/fchem.2021.669452