Biophysical Society Conference | Tahoe 2023

Proton Reactions: From Basic Science to Biomedical Applications

Monday Speaker Abstracts

THE VOLTAGE-GATED PROTON CHANNEL DISCOVERS ITS FAMILY Boris Musset 1 ; 1 PMU Nuremberg, Center of Physiology, Pathophysiology and Biophysics, Nuremberg, Germany A little more than four decades ago, the first voltage-clamp recording of the voltage-gated proton channel triggered a novel research field. Almost two and a half decades later, the discovery of the channel's gene initiated further progress in elucidating the biophysical properties, structure, function, and physiology of this unique channel. Despite this, the proton channel field continues to evolve, presenting numerous unanswered questions. One of the hallmarks of the voltage-gated proton channel was that each species so far detected held solely one gene coding for the proton channel. Here, we present the discovery and characterization of three independent genes coding for distinct proton channels, in a single species. Aplysia californica, a classical model organism of neural plasticity, harbours these genes. Additionally, we present our advances in the structure and function of the proton channel, by iteratively combining molecular dynamics simulations with patch-clamp recordings, specifically targeting the proton channel gating mechanism. Lastly, we suggest a potential path for the evolution of the voltage-gated proton channel. HOW A MULTIPLICITY OF PROTONATION STATES IN PROTEINS SUPPORTS PROTON TRANSFERS Marilyn Gunner 1 ; Junjun Mao 1 ; Umesh Khaniya 1 ; Gehan Ranapura 1 ; Rongmei Wei 2 ; Jose Ortiz-Soto 2 ; Md. Raihan Uddin 3 ; 1 City College of New York CUNY, Physics, New York, NY, USA 2 City College of New York CUNY, Chemistry, New York, NY, USA 3 City College of New York CUNY, Biochemistry, New York, NY, USA Proteins are known to exist in a distribution of conformations, but the complexity of the distribution of protonation states in the equilibrium ensemble is under-appreciated. Recent developments in the MCCE program have enabled the analysis of protonation and conformation microstates in Monte Carlo sampling, providing insight into the diversity of protonation states at equilibrium. The individual microstates, which define the protonation states and conformation of each residue and ligand are akin to an MD snapshot. Analysis of these states reveals how protons move within complex clusters of buried protonatable residues that make up proton loading sites. The proton coupled electron transfers in photosynthetic reaction centers, cytochrome c oxidase and complex I provide examples of how the protonation and conformation microstates influence site redox potentials, proton affinities of proton loading sites and the connectivity of extended proton transfer pathways.

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