A universal coupling mechanism of respiratory complex I

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• Complex I is crucial for cellular energy production, catalyzing electron transfer and proton translocation.
• The precise mechanism coupling these processes in Complex I remains incompletely understood.

Purpose of the Study:

• To elucidate the coupling mechanism of Complex I using structural and functional analyses.
• To present a novel mechanism for proton translocation and energy coupling in Complex I.

Main Methods:

• Cryo-electron microscopy (cryo-EM) to determine structures of Escherichia coli Complex I (EcCI) in various redox states.
• Analysis of EcCI during catalytic turnover to observe dynamic conformational changes.
• Mutagenesis studies to validate the proposed mechanism.

Main Results:

• EcCI predominantly exists in an open state, facilitating quinone access and movement.
• The transition to a closed state occurs during turnover, revealing genuine catalytic intermediates.
• A 'domino effect' mechanism involving proton transfers and electrostatic interactions explains proton pumping and ejection from the NuoL subunit.

Conclusions:

• The study proposes a robust and universal mechanism for Complex I energy coupling.
• The findings clarify the role of conformational changes and proton transfer pathways.
• This work provides insights into the function of Complex I and related enzymes in energy metabolism.