9TAJ

E. coli Complex I WT purified in LMNG

Summary for 9TAJ

• Entry DOI: 10.2210/pdb9taj/pdb
• EMDB information: 55748
• Descriptor: NADH-quinone oxidoreductase subunit E, NADH-quinone oxidoreductase subunit M, NADH-quinone oxidoreductase subunit A, ... (23 entities in total)
• Functional Keywords: proton transport, bioenergetics
• Biological source: Escherichia coli BW25113; More
• Total number of polymer chains: 13
• Total formula weight: 562960.45

Authors

Kovalova, T.,Beghiah, A.,Kaila, V.R.I. (deposition date: 2025-11-18, release date: 2026-05-06, Last modification date: 2026-07-15)

Primary citation

Beghiah, A.,Saura, P.,Kovalova, T.,Hoeser, F.,Friedrich, T.,Kaila, V.R.I.
A carboxylate switch point controls long-range energy transduction in respiratory Complex I.
Nat Commun, 17:-, 2026

PubMed Abstract: Complex I is a highly intricate membrane-bound protein complex that powers the cellular energy metabolism by a long-range ( > 300 Å) proton-coupled electron transfer (PCET) reaction. Here, we investigate the highly debated coupling mechanism of Complex I by probing the charge transfer reaction along its functionally central carboxylate pathway (E-channel). By combining biophysical and site-directed mutagenesis experiments with high-resolution (2.6-2.8 Å) cryo-electron microscopy (cryo-EM) and multiscale simulations, we identify a conserved carboxylate switch point (D79) that mediates proton transfer by establishing a kinetic gate and couples the redox chemistry to proton pumping. We find that mutation of the identified site, as found in patients suffering from severe neurodegenerative disorders, drastically perturbs the charge transfer mechanism, and results in a 20% PCET activity. Our combined findings illustrate mechanistic principles of molecular gates underlying long-range charge transfer reactions, and show how disease mutations perturb the function of conserved switch points in energy transduction.

PubMed: 42386739
DOI: 10.1038/s41467-026-74767-6

Experimental method

ELECTRON MICROSCOPY (3 Å)