Section Head:
Sergey M. Bezrukov, Ph.D.

We study physical principles that govern channel-facilitated transport of metabolites and other large solutes across cell and organelle membranes. Channel-forming membrane proteins respond to their immediate environment such as surrounding lipids, solution composition, local acidity, etc. In order to study channels under precisely controlled conditions, we reconstitute these proteins into planar lipid bilayers. The proteins and polypeptides we work with include: VDAC (Voltage-Dependent Anion Channel from the outer membrane of mitochondria), OmpF (general bacterial porin), OprF (major non-specific porin of Pseudomonas aeruginosa), Maltoporin (sugar-specific bacterial porin), a -Hemolysin (toxin from Staphylococcus aureus), Alamethicin (amphiphilic peptide toxin from Trichoderma viride), Syringomycin E (lipopeptide toxin from Pseudomonas syringae), and PA 63 (Protective Antigen from Bacillus anthracis ). These all form “large” channels with aqueous pores of ≥ 1 nm diameter.

Emerging evidence demonstrates that most of these large channels, rather than being merely "general diffusion pores," are structures highly specialized for the solutes they allow to pass. One of our main goals is to reveal the mechanisms of channel selectivity to solutes other than small ions. This knowledge will advance our understanding of the molecular interactions that regulate metabolite flux under normal conditions and in pathology.