7XK4

Cryo-EM structure of Na+-pumping NADH-ubiquinone oxidoreductase from Vibrio cholerae, state 2

Summary for 7XK4

• Entry DOI: 10.2210/pdb7xk4/pdb
• EMDB information: 33243
• Descriptor: Na(+)-translocating NADH-quinone reductase subunit A, DODECYL-BETA-D-MALTOSIDE, FE2/S2 (INORGANIC) CLUSTER, ... (13 entities in total)
• Functional Keywords: nadh-quinone oxidoreductase, redox-driven sodium pump, bioenergetics, vibrio cholerae, electron transport, membrane protein complex, oxidoreductase, translocase
• Biological source: Vibrio cholerae O395; More
• Total number of polymer chains: 6
• Total formula weight: 216976.76

Authors

Kishikawa, J.,Ishikawa, M.,Masuya, T.,Murai, M.,Barquera, B.,Miyoshi, H. (deposition date: 2022-04-19, release date: 2022-07-20, Last modification date: 2022-08-10)

Primary citation

Kishikawa, J.I.,Ishikawa, M.,Masuya, T.,Murai, M.,Kitazumi, Y.,Butler, N.L.,Kato, T.,Barquera, B.,Miyoshi, H.
Cryo-EM structures of Na + -pumping NADH-ubiquinone oxidoreductase from Vibrio cholerae.
Nat Commun, 13:4082-4082, 2022

PubMed Abstract: The Na-pumping NADH-ubiquinone oxidoreductase (Na-NQR) couples electron transfer from NADH to ubiquinone with Na-pumping, generating an electrochemical Na gradient that is essential for energy-consuming reactions in bacteria. Since Na-NQR is exclusively found in prokaryotes, it is a promising target for highly selective antibiotics. However, the molecular mechanism of inhibition is not well-understood for lack of the atomic structural information about an inhibitor-bound state. Here we present cryo-electron microscopy structures of Na-NQR from Vibrio cholerae with or without a bound inhibitor at 2.5- to 3.1-Å resolution. The structures reveal the arrangement of all six redox cofactors including a herein identified 2Fe-2S cluster located between the NqrD and NqrE subunits. A large part of the hydrophilic NqrF is barely visible in the density map, suggesting a high degree of flexibility. This flexibility may be responsible to reducing the long distance between the 2Fe-2S centers in NqrF and NqrD/E. Two different types of specific inhibitors bind to the N-terminal region of NqrB, which is disordered in the absence of inhibitors. The present study provides a foundation for understanding the function of Na-NQR and the binding manner of specific inhibitors.

PubMed: 35882843
DOI: 10.1038/s41467-022-31718-1

Experimental method

ELECTRON MICROSCOPY (3.1 Å)