The coupling mechanism of respiratory complex I - a structural and evolutionary perspective

Area of Science:

• Biochemistry
• Molecular Biology
• Evolutionary Biology

Background:

• Complex I is a vital enzyme in the respiratory chain, essential for energy production in many organisms.
• Its evolutionary origin involves the integration of pre-existing hydrogenase and transporter modules.
• Understanding its structure and function is key to comprehending cellular respiration.

Purpose of the Study:

• To reanalyze evolutionarily related complexes using recent crystallographic data of Complex I.
• To investigate the evolutionary origins and mechanisms of oxidoreduction-coupled ion translocation.
• To propose a detailed model for the reversible coupling mechanism of Complex I.

Main Methods:

• Analysis of recently determined crystallographic structures of Complex I.
• Comparative structural analysis of Complex I with related hydrogenases and formate dehydrogenlyases.
• Investigation of quinone oxidoreduction properties in relation to Complex I structure.

Main Results:

• Identified structural homology between the electron input module of formate dehydrogenlyases and Complex I subunit NuoG.
• Proposed that Complex I-related hydrogenases operate via a conformation-driven mechanism.
• Located the conserved coupling site at the interface of subunits NuoB/D/H, suggesting a single origin of coupling.
• Suggested a fully reversible coupling mechanism based on structural and quinone oxidoreduction data.

Conclusions:

• The evolutionary unification of modules and the origin of coupling occurred early in Complex I's history.
• The proposed reversible coupling mechanism involves protein-controlled proton access and ubiquinol charge-driven conformational changes.
• This study provides new insights into the structure-function relationship and evolutionary path of Complex I.