Work

Molecular Principles of Gating Proton Transport in the Antiporter Modules of Respiratory Complex I

Year: 2026

Type: article

Abstract: The respiratory Complex I is a highly intricate redox-driven proton pump that powers oxidative phosphorylation across all domains of life. Yet, despite major efforts, its long-range energy transduction principles remain much debated. Here, we study the molecular principles of proton transport by engineering the antiporter modules of Complex I. By combining directed mutagenesis with time-resolved spectroscopy and molecular dynamics (MD) simulations, we identify conserved residues along the proton channels that control the rate of proton transfer across proteoliposome membranes. The antiporter modules catalyze this tightly regulated proton transport by transient water wires that follow intrinsic electric fields along the proton channels. Based on MD simulations, we identify conserved gating sites, established by nonpolar residues, which modulate the hydration and electric field effects underlying the proton transport upon mutation. On a general level, our findings highlight how the modular energy-transduction machinery of Complex I employs a combination of electrostatic and conformational coupling principles to catalyze long-range proton transport, with distinct similarities to other enzymes.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.6c05956

Authors: Sofia Badolato, Sarah C. Rossmann, Joana Pereira, Hyunho Kim, Ville R. I. Kaila

Institution: Stockholm University

Language: English

Topic: Protein Structure and Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $4,500

Funders: Göran Gustafssons Stiftelser, Göran Gustafssons Stiftelse för Naturvetenskaplig och Medicinsk Forskning, Knut och Alice Wallenbergs Stiftelse, Vetenskapsrådet