Molecular Evolution of Alternative Oxidase Proteins: A Phylogenetic and Structure Modeling Approach.
Alternative oxidases (AOXs) are mitochondrial cyanide-resistant membrane-bound metallo-proteins catalyzing the oxidation of ubiquinol and the reduction of oxygen to water bypassing two sites of proton pumping, thus dissipating a major part of redox energy into heat. Here, the structure of Arabidopsis thaliana AOX 1A has been modeled using the crystal structure of Trypanosoma brucei AOX as a template. Analysis of this model and multiple sequence alignment of members of the AOX family from all kingdoms of Life indicate that AOXs display a high degree of conservation of the catalytic core, which is formed by a four-α-helix bundle, hosting the di-iron catalytic site, and is flanked by two additional α-helices anchoring the protein to the membrane. Plant AOXs display a peculiar covalent dimerization mode due to the conservation in the N-terminal region of a Cys residue forming the inter-monomer disulfide bond. The multiple sequence alignment has also been used to infer a phylogenetic tree of AOXs whose analysis shows a polyphyletic origin for the AOXs found in Fungi and a monophyletic origin of the AOXs of Eubacteria, Mycetozoa, Euglenozoa, Metazoa, and Land Plants. This suggests that AOXs evolved from a common ancestral protein in each of these kingdoms. Within the Plant AOX clade, the AOXs of monocotyledon plants form two distinct clades which have unresolved relationships relative to the monophyletic clade of the AOXs of dicotyledonous plants. This reflects the sequence divergence of the N-terminal region, probably due to a low selective pressure for sequence conservation linked to the covalent homo-dimerization mode.
['Pennisi|Rosa|R|', 'Salvi|Daniele|D|', 'Brandi|Valentina|V|', 'Angelini|Riccardo|R|', 'Ascenzi|Paolo|P|', 'Polticelli|Fabio|F|']
D000595:Amino Acid Sequence D017360:Arabidopsis D020134:Catalytic Domain D017124:Conserved Sequence D019143:Evolution, Molecular D024101:Mitochondrial Proteins D008958:Models, Molecular D010084:Oxidation-Reduction D010088:Oxidoreductases D010802:Phylogeny D010940:Plant Proteins D010944:Plants D011487:Protein Conformation D016415:Sequence Alignment D013329:Structure-Activity Relationship D014346:Trypanosoma brucei brucei
Molecular evolution Alternative oxidase Molecular modeling Phylogenetic analysis