Respiratory complex I: 'steam engine' of the cell?

Area of Science:

• Biochemistry
• Structural Biology
• Molecular Biology

Background:

• Complex I is the initial enzyme in the respiratory chain, essential for cellular energy production.
• It is implicated in human neurodegenerative diseases and aging processes.
• Complex I is a large, L-shaped membrane protein complex with distinct hydrophilic and membrane domains.

Purpose of the Study:

• To elucidate the complete structure of Complex I, including its membrane domain and overall architecture.
• To compare the structures of bacterial and mitochondrial Complex I.
• To understand the mechanism of proton translocation coupled to electron transfer.

Main Methods:

• X-ray crystallography was used to determine the structures of the hydrophilic domain and the complete bacterial complex.
• Previous structural data of the hydrophilic domain in various redox states were utilized.
• X-ray analysis was also performed on the larger mitochondrial enzyme.

Main Results:

• The complete architecture of the membrane domain and the entire bacterial Complex I was described.
• X-ray analysis of the mitochondrial enzyme provided further structural insights.
• Core subunits of bacterial and mitochondrial Complex I exhibit highly similar structures.
• A mechanism involving long-range conformational changes, coordinated by a long α-helix, was proposed for coupling electron transfer to proton translocation.

Conclusions:

• Significant progress has been made in understanding the complete structure of Complex I.
• Bacterial and mitochondrial Complex I share conserved core subunit structures.
• A 'coupling rod' mechanism involving conformational changes is proposed for energy transduction in Complex I.