A long-standing mystery in bacterial bioenergetics is beginning to unravel as researchers capture fleeting structural states of a sodium-pumping enzyme in action.
The enzyme Na⁺-NQR acts as a sodium pump that fuels respiration in many marine and disease-causing bacteria. It relies on redox reactions, which involve the transfer of electrons between molecules, to move sodium ions across the cell membrane. This process helps sustain bacterial growth.
Despite its importance, the exact mechanism has remained unclear. Researchers have struggled to determine how electron transfer is directly connected to sodium transport. A major obstacle has been the lack of detailed structural data on the short-lived intermediate states that appear while the enzyme is active. Without this information, it has been difficult to fully explain how the pump operates.
To address this, a research team at Kyoto University set out to investigate the system in greater detail. Using cryo-electron microscopy, co-first author Moe Ishikawa-Fukuda captured a series of intermediate structures as the enzyme changed shape during activity. These images were then paired with molecular dynamics simulations conducted by co-first author Takehito Seki, allowing the team to analyze both structure and motion.
Linking Electron Transfer to Ion Transport
The simulations showed that electron transfer within the protein triggers structural shifts in the enzyme. These changes control a gate embedded in the membrane, which opens and closes to allow sodium ions to pass through the cell membrane.
“Our study is the first to clearly explain how redox reactions directly drive sodium ion transport at the molecular level, providing a new framework for understanding energy conversion in bacteria,” says Ishikawa-Fukuda.
The team also identified an unexpected contributor to their findings: a compound called korormicin, previously studied by the group. This inhibitor proved essential for stabilizing and capturing key intermediate states that are normally too fleeting to observe.
“Understanding redox-driven sodium pumping addresses a long-standing question in bioenergetics, revealing a strategy that is fundamentally different from the proton pump found in mammalian mitochondria,” says Seki.
Toward Future Applications
Looking ahead, the researchers plan to explore whether these newly identified structural states can be targeted to shut down the sodium pump. Such an approach could lead to new types of antibiotics that act on previously untapped biological systems.
“Our goal was to understand how this sodium pump works at a fundamental level,” says team leader Masatoshi Murai. “Although this is basic research, we hope that clarifying these mechanisms will eventually contribute to the development of new strategies to combat pathogenic bacteria.”
Reference: “The redox driven Na+-pumping mechanism in Vibrio cholerae NADH-quinone oxidoreductase relies on dynamic conformational changes” by Moe Ishikawa-Fukuda, Takehito Seki, Jun-ichi Kishikawa, Takahiro Masuya, Kei-ichi Okazaki, Takayuki Kato, Blanca Barquera, Hideto Miyoshi and Masatoshi Murai, 12 February 2026, Nature Communications.
DOI: 10.1038/s41467-026-69182-w
This work is a collaboration with Rensselaer Polytechnic Institute researchers and is supported by an NIH grant. Team members also include researchers from the Kyoto Institute of Technology and the Institute for Molecular Science.
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