Accelerated Evolution of Cytochrome <i>c</i> in Higher Primates, and Regulation of the Reaction between Cytochrome <i>c</i> and Cytochrome Oxidase by Phosphorylation
Cytochrome <i>c</i> (Cc) underwent accelerated evolution from the stem of the anthropoid primates to humans. Of the 11 amino acid changes that occurred from horse Cc to human Cc, five were at Cc residues near the binding site of the Cc:CcO complex. Single-point mutants of horse and human...
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2022-12-01
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| author | Sue Ellen Brand Martha Scharlau Lois Geren Marissa Hendrix Clayre Parson Tyler Elmendorf Earl Neel Kaila Pianalto Jennifer Silva-Nash Bill Durham Francis Millett |
| author_facet | Sue Ellen Brand Martha Scharlau Lois Geren Marissa Hendrix Clayre Parson Tyler Elmendorf Earl Neel Kaila Pianalto Jennifer Silva-Nash Bill Durham Francis Millett |
| author_sort | Sue Ellen Brand |
| collection | DOAJ |
| description | Cytochrome <i>c</i> (Cc) underwent accelerated evolution from the stem of the anthropoid primates to humans. Of the 11 amino acid changes that occurred from horse Cc to human Cc, five were at Cc residues near the binding site of the Cc:CcO complex. Single-point mutants of horse and human Cc were made at each of these positions. The Cc:CcO dissociation constant K<sub>D</sub> of the horse mutants decreased in the order: T89E > native horse Cc > V11I Cc > Q12M > D50A > A83V > native human. The largest effect was observed for the mutants at residue 50, where the horse Cc D50A mutant decreased K<sub>D</sub> from 28.4 to 11.8 μM, and the human Cc A50D increased K<sub>D</sub> from 4.7 to 15.7 μM. To investigate the role of Cc phosphorylation in regulating the reaction with CcO, phosphomimetic human Cc mutants were prepared. The Cc T28E, S47E, and Y48E mutants increased the dissociation rate constant k<sub>d</sub>, decreased the formation rate constant k<sub>f</sub>, and increased the equilibrium dissociation constant K<sub>D</sub> of the Cc:CcO complex. These studies indicate that phosphorylation of these residues plays an important role in regulating mitochondrial electron transport and membrane potential ΔΨ. |
| first_indexed | 2024-03-09T17:13:21Z |
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| id | doaj.art-60c0654cabbb4f038c731df6eb77afda |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T17:13:21Z |
| publishDate | 2022-12-01 |
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| series | Cells |
| spelling | doaj.art-60c0654cabbb4f038c731df6eb77afda2023-11-24T13:54:22ZengMDPI AGCells2073-44092022-12-011124401410.3390/cells11244014Accelerated Evolution of Cytochrome <i>c</i> in Higher Primates, and Regulation of the Reaction between Cytochrome <i>c</i> and Cytochrome Oxidase by PhosphorylationSue Ellen Brand0Martha Scharlau1Lois Geren2Marissa Hendrix3Clayre Parson4Tyler Elmendorf5Earl Neel6Kaila Pianalto7Jennifer Silva-Nash8Bill Durham9Francis Millett10North Murray High School, Chatsworth, GA 30705, USADepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, USADepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, USAIndependent Researcher, P.O. Box 603, Dardanelle, AR 72834, USADepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, USASchool of Medicine, University of Kansas Medical Center, 2060 W 39th Ave, Kansas City, KS 66103, USATulsa Bone and Joint Associates, Tulsa, OK 74146, USADepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, USAIndependent Researcher, 5 Kingdom Court, Maumelle, AR 72113, USADepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, USADepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, USACytochrome <i>c</i> (Cc) underwent accelerated evolution from the stem of the anthropoid primates to humans. Of the 11 amino acid changes that occurred from horse Cc to human Cc, five were at Cc residues near the binding site of the Cc:CcO complex. Single-point mutants of horse and human Cc were made at each of these positions. The Cc:CcO dissociation constant K<sub>D</sub> of the horse mutants decreased in the order: T89E > native horse Cc > V11I Cc > Q12M > D50A > A83V > native human. The largest effect was observed for the mutants at residue 50, where the horse Cc D50A mutant decreased K<sub>D</sub> from 28.4 to 11.8 μM, and the human Cc A50D increased K<sub>D</sub> from 4.7 to 15.7 μM. To investigate the role of Cc phosphorylation in regulating the reaction with CcO, phosphomimetic human Cc mutants were prepared. The Cc T28E, S47E, and Y48E mutants increased the dissociation rate constant k<sub>d</sub>, decreased the formation rate constant k<sub>f</sub>, and increased the equilibrium dissociation constant K<sub>D</sub> of the Cc:CcO complex. These studies indicate that phosphorylation of these residues plays an important role in regulating mitochondrial electron transport and membrane potential ΔΨ.https://www.mdpi.com/2073-4409/11/24/4014Cytochrome <i>c</i>Cytochrome <i>c</i> oxidaseelectron transferphosphorylation |
| spellingShingle | Sue Ellen Brand Martha Scharlau Lois Geren Marissa Hendrix Clayre Parson Tyler Elmendorf Earl Neel Kaila Pianalto Jennifer Silva-Nash Bill Durham Francis Millett Accelerated Evolution of Cytochrome <i>c</i> in Higher Primates, and Regulation of the Reaction between Cytochrome <i>c</i> and Cytochrome Oxidase by Phosphorylation Cells Cytochrome <i>c</i> Cytochrome <i>c</i> oxidase electron transfer phosphorylation |
| title | Accelerated Evolution of Cytochrome <i>c</i> in Higher Primates, and Regulation of the Reaction between Cytochrome <i>c</i> and Cytochrome Oxidase by Phosphorylation |
| title_full | Accelerated Evolution of Cytochrome <i>c</i> in Higher Primates, and Regulation of the Reaction between Cytochrome <i>c</i> and Cytochrome Oxidase by Phosphorylation |
| title_fullStr | Accelerated Evolution of Cytochrome <i>c</i> in Higher Primates, and Regulation of the Reaction between Cytochrome <i>c</i> and Cytochrome Oxidase by Phosphorylation |
| title_full_unstemmed | Accelerated Evolution of Cytochrome <i>c</i> in Higher Primates, and Regulation of the Reaction between Cytochrome <i>c</i> and Cytochrome Oxidase by Phosphorylation |
| title_short | Accelerated Evolution of Cytochrome <i>c</i> in Higher Primates, and Regulation of the Reaction between Cytochrome <i>c</i> and Cytochrome Oxidase by Phosphorylation |
| title_sort | accelerated evolution of cytochrome i c i in higher primates and regulation of the reaction between cytochrome i c i and cytochrome oxidase by phosphorylation |
| topic | Cytochrome <i>c</i> Cytochrome <i>c</i> oxidase electron transfer phosphorylation |
| url | https://www.mdpi.com/2073-4409/11/24/4014 |
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