How dynamics in hydrogen-bonding networks define proton channel selectivity and conductivity

TL;DR

This paper explores how hydrogen-bonding networks in proton channels enable selective and efficient proton transport across cell membranes.

Contribution

The study presents de novo designed proton channels that reveal the role of protein-water interactions in proton selectivity and conductivity.

Findings

Dynamic interactions between water and protein sidechains are essential for proton selectivity.

Designed proton channels demonstrate how these interactions enhance transport efficiency.

The results emphasize the importance of considering dynamics in biomolecular system design.

Abstract

The precise transport of protons across cellular membranes is key for many biocatalytic and bioenergetic processes. Proton channels facilitate the selective and efficient movement of protons for all necessary functions while maintaining membrane fidelity and preventing ion leakage. The dynamics of interlumenal waters and pore-lining sidechains, among other features, define the ability of these channels to selectively and rapidly transport protons. Through the de novo design of functional proton channels, we reveal how specific protein-water interactions contribute to proton transport, providing new insights into the dynamics necessary for proton-selective transport. These findings underscore the critical role of dynamic interactions in achieving both selectivity and efficiency, highlighting the need to explicitly consider these features in the design of proton channels and other biomolecular systems for tailored functionality.