Electron Transfer Coupled to Conformational Dynamics in Cell Respiration.

Area of Science:

• Biochemistry
• Molecular Biology
• Bioenergetics

Background:

• Cellular respiration generates energy via electron transport chains.
• Cytochrome c oxidase (CcO) is the terminal enzyme, coupling redox reactions to proton pumping for ATP synthesis.
• The precise mechanism linking electron transfer to proton pumping in mammalian CcO remains incompletely understood.

Purpose of the Study:

• To investigate the role of a conserved dynamic region in transmembrane helix X of CcO subunit I.
• To determine if this region couples electron transfer to proton translocation in mammalian CcO.
• To compare the function of this region in yeast and bovine CcO.

Main Methods:

• Generation of yeast CcO mutants (V380M and G384D) in helix X.
• Assessment of respiratory deficiency and CcO turnover in mutant strains.
• Long-timescale atomistic molecular dynamics simulations of wild-type and mutant bovine and yeast CcOs.

Main Results:

• Yeast CcO mutants exhibited respiratory deficiency due to inhibited intra-protein electron transfer and CcO turnover.
• Molecular dynamics simulations revealed redox- and mutation-dependent conformational changes in the TMH X span.
• These dynamic changes in helix X were observed in both bovine and yeast CcO.

Conclusions:

• The dynamic module within TMH X plays a critical role in optimizing intra-protein electron transfer in CcO.
• Conformational flexibility in this region is essential for efficient CcO function.
• This finding provides insights into the mechanistic differences between mammalian and bacterial CcO.