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Review
. 2023 Mar 29;24(7):6428.
doi: 10.3390/ijms24076428.

Interaction of Terminal Oxidases with Amphipathic Molecules

Natalia V Azarkina  1 , Vitaliy B Borisov  1 , Ilya P Oleynikov  1 , Roman V Sudakov  1 , Tatiana V Vygodina  1
Affiliations
Review

Interaction of Terminal Oxidases with Amphipathic Molecules

Natalia V Azarkina et al. Int J Mol Sci. .

Abstract

The review focuses on recent advances regarding the effects of natural and artificial amphipathic compounds on terminal oxidases. Terminal oxidases are fascinating biomolecular devices which couple the oxidation of respiratory substrates with generation of a proton motive force used by the cell for ATP production and other needs. The role of endogenous lipids in the enzyme structure and function is highlighted. The main regularities of the interaction between the most popular detergents and terminal oxidases of various types are described. A hypothesis about the physiological regulation of mitochondrial-type enzymes by lipid-soluble ligands is considered.

Keywords: amphipathic ligands; bile acid-binding site; cytochrome oxidase; detergents; molecular bioenergetics; regulation; terminal oxidases; tight bound lipids.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Structure of the type A heme–copper terminal oxidases with tightly bound lipids. 3D structures of dimeric cytochrome c oxidase (CcO) from bovine heart mitochondria (PBD entry 3ASO; green) and CcO from Rhodobacter sphaeroides (PBD entry 1M56; grey) are superimposed. Lipids are shown by sticks in the corresponding colors, with oxygen (red), nitrogen (blue) and phosphorus (orange) highlighted. (A) Side view, matrix is at the bottom. Near the outer membrane’s surface, mutually perpendicular planes of hemes a and a3 are seen, as well as the copper centers (binuclear CuA and mononuclear CuB, brown spheres). (B) View from the outer surface of the membrane. (C) Enlarged part of (B). Subunit III is located on the right side of the image.
Figure 2
Figure 2
BABS with the ligand and adjacent endogenous lipid. (A) The BABS region from the mitochondrial dimeric CcO structure (PDB entry 5B1A) is depicted as a protein surface. The endogenous phosphatidylethanolamine molecule is shown by dark green sticks. Decyl maltoside (brown sticks) from R. sphaeroides’s CcO structure (PDB entry 3DTU) is superimposed on the image in the appropriate location. The cholate molecule (grey sticks) is bound in the hydrophobic cavity formed by subunits I, II and VIa (from the opposite monomer). Side view, matrix is at the bottom. Oxygen and nitrogen atoms are colored in red and blue, respectively. (B) The same (except for the detergent from the bacterial enzyme structure), but enlarged. The residues of subunit VIa, presumably involved in interactions with cholate (Arg14, Arg17, Phe18 and Phe21), are indicated and tinted in white.
Figure 3
Figure 3
Binding sites for amphipathic ligands in mitochondrial CcO. (A) Side view. (B) View from the inner membrane surface. The structures of the dimer (formed by light green and a deep green monomers; PDB entry 3ASO) and the monomer (cyan; PDB entry 5Z62) are superimposed. In the center of the image in (B), one can see the NDUFA4 subunit, which is present only in the monomeric structure and is involved in the regulation of the monomer–dimer transition [56]. Lipids are grey, with red O and blue N atoms. BABS is marked by E62II, colored in purple. SBSM is marked by M278I, colored in orange. The distance between E62II and M278I (yellow dashed line) is 20 Å. The cholate bound in BABS is grey with red oxygens. The distance from cholate’ hydroxyl 7 to carboxyl of E62II is 2.8 Å, and the nearest distance from the cholate to M278I is about 8 Å.
See this image and copyright information in PMC

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