A piston proton pump

Courtesy of Rouslan Efremov, Rikke Schmidt Kjaergaard, and Leonid Sazanov

The paper

R.G. Efremov et al., “The architecture of respiratory complex I,” Nature, 465:441–45, 2010. http://bit.ly/protonpump

The finding

Although the molecular machines that power ATP synthesis via trans-membrane proton gradients are well known, how the gradient is created in the first place is more mysterious. Now, a crystal structure of complex I, the first group of proteins involved in generating energy from the oxidation of glucose, shows how it uses unusual piston-shaped molecules to pump protons across the membrane.

The surprise

The mechanism proposed by Leonid Sazanov’s group at the Medical Research Council in Cambridge is “almost completely unexpected,” says Faculty Member Thomas Meier. Unlike the ATP synthase, which “drives protons across the membrane in a rotary turbine-like motion,” writes Faculty member Nathan Nelson in his review, the transfer of electrons from NADH cause a...

The impact

Scientists have puzzled about the pumping mechanism of complex I for years. Faculty Member Andrea Mattevi predicts that it will become one of the most cited papers in respiratory chain research, as important to our complete understanding of energy generation as is the mechanism of ATP synthase.

The next step

Sazanov’s next task, he says, is to improve the structural resolution from the protein crystals and make site-specific mutations to verify the proposed mechanism, and to understand precisely how complex I contributes to neurodegenerative disorders such as Parkinson’s.

F1000 evaluators: N. Nelson (Tel Aviv Univ.) • A. Mattevi (Univ. of Pavia) • T. Frey (San Diego State Univ.) • R. Carter (Nat. Inst. for Arthritis and Musculoskeletal and Skin Diseases) •
T. Meier (Max Planck Inst. of Biophysics)

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