Researchers Reveal Molecular Mechanism of Novel Heme-copper Terminal Oxidase Utilizing Two Electron Donors (Biology)

The heme-copper terminal oxidases (HCOs) superfamily, one of the most important metalloproteinases, is responsible for the efficient electron transfer from cytochrome c or quinol to molecular oxygen. The members of this family are multi-subunit complexes. In the complex, there is a conserved central catalytic subunit I, containing two heme groups and a copper atom (CuB), and the active site is formed by one high-spin heme and CuB. Subunit II usually contains binuclear CuA center.

Cytochrome c oxidase (CcO) family belongs to the HCOs superfamily, but could only use cytochrome c as electron donor according to previous studies. Recently, a novel CcO from the hyperthermophilic bacterium Aquifex aeolicus (AaCcO) was discovered to be able to use both cytochrome c and naphthoquinol (NQ) as electron donors, but its molecular mechanism as well as the evolutionary significance are still unknown.

In a study published online in Angewandte Chemie International Edition, the researchers from SUN Fei’s group at Institute of Biophysics of the Chinese Academy of Sciences, and Hartmut Michel’s group at Max Planck Institute of Biophysics, solved the 3.4 Å resolution electron cryo-microscopic structure of AaCcO.

AaCcO forms a novel dimeric structure mediated by subunit I (CoxA2), and different from that of all other reported CcO dimers.

The researchers observed fruitful protein-lipid interactions in the dimeric interface and found a novel substrate binding site of the NQ at the dimeric interface, which could allow NQ be a direct electron donor bypassing cytochrome c. As a result, it seems that AaCcO dimer should be the necessary condition for direct electron transfer from NQ.

Moreover, they found that the adapted structure of AaCcO has only one available proton pathway (K pathway) and a V-shaped unobstructed oxygen channel with more hydrophobic residues blocking one entry, which appeared to be evolutionary advantageous to keep the balance between its enzymatic activity and structural stability in the hyperthermophilic environment.

These results provide structural basis for molecular mechanism and the evolutionary significance of CcOs in the extreme thermal environment.


The unusual homodimer of a heme-copper terminal oxidase allows itself to utilize two electron donors

Provided by Chinese Academy of Sciences

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