Structure of an Ancient Respiratory System

Area of Science:

• Biochemistry
• Structural Biology
• Microbiology

Background:

• Membrane-bound hydrogenase (MBH) and complex I are homologous respiratory enzymes.
• A detailed structural understanding of their evolutionary relationship has been missing.

Purpose of the Study:

• To elucidate the cryo-electron microscopy (cryo-EM) structure of a 14-subunit MBH from Pyrococcus furiosus.
• To provide a structural basis for the evolutionary connection between MBH and complex I.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was used to determine the structure of MBH.
• Comparative structural analysis was performed between MBH and complex I.

Main Results:

• The MBH structure reveals a membrane-anchored hydrogenase module similar to complex I's Q-module.
• The ion-translocation module features distinct H+ and Na+ translocating units.
• The Na+ translocating unit, absent in complex I, facilitates hydrogen evolution and Na+ gradient formation for ATP synthesis at high temperatures.

Conclusions:

• The MBH structure clarifies its evolutionary relationship with complex I, despite architectural differences.
• MBH utilizes a unique Na+ gradient mechanism for ATP synthesis in hyperthermophilic conditions.
• Insights into Mrp antiporter structure and MBH evolution are provided.