Biophysical Society Conference | Tahoe 2023

Proton Reactions: From Basic Science to Biomedical Applications

Tuesday Speaker Abstracts

INTERFACIAL PROTON DIFFUSION Anna Maznichenko 1 , Stefania Brescia 1 , Peter Pohl 1 1 Johannes Kepler University Linz, Austria

Proton diffusion along biological membranes may be essential for many transport processes. Instead of using proton-relaying lipid or proteinaceous moieties, the interfacial protons appear to use surface water molecules for rapid migration. Long-range interfacial diffusion is facilitated by a substantial Gibbs activation energy barrier ΔG ‡ r , which opposes the release of protons from the surface to the bulk. ΔG ‡ r contains only a minor enthalpic contribution ΔG ‡ H roughly equivalent to the breakage of a single hydrogen bond. Introducing a negative net charge into the bilayer doubled ΔG ‡ H , whereas positive net charges decreased ΔG ‡ H (1). We observed significant changes in ΔG ‡ r ’s major entropic component ΔG ‡ s when introducing uncharged surface moieties capable of influencing the water orientation at the bilayer surface. Modulation of ΔG ‡ r by altering membrane composition may be essential for the regulation proton channels, pumps, and transporters. Here we focused on the proton channel H V 1, which provides dynamic water-mediated lipid-protein hydrogen-bonded networks at its mouth. In contrast to protons migrating at the membrane surface, the intraluminal protons use at least one proton-relaying amino acid moiety to cross the channel (2). This residue occludes the channel, interrupting the chain of water molecules. As a result, the open H V 1 channel is impermeable to water, and the rate of proton transport is reduced. The research was supported by the European Union’s Horizon 2020 Research and Innovation Program under the Marie Sklodowska-Curie grant agreement No 860592, Innovative Training Network ‘Proton and proton-coupled transport’. 1. Weichselbaum et al. (2023). Biomolecules 13:352 2. Boytsov et al. (2023) Small 19:2205968

27