Tryptophan Oxidation in the UQCRC1 Subunit of Mitochondrial Complex III (Ubiquinol-Cytochrome C Reductase) in a Mouse Model of Myodegeneration Causes Large Structural Changes in the Complex: A Molecular Dynamics Simulation Study
| العنوان: | Tryptophan Oxidation in the UQCRC1 Subunit of Mitochondrial Complex III (Ubiquinol-Cytochrome C Reductase) in a Mouse Model of Myodegeneration Causes Large Structural Changes in the Complex: A Molecular Dynamics Simulation Study |
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| المؤلفون: | Sruthi Unni, Saravanamuthu Thiyagarajan, M.M. Srinivas Bharath, Balasundaram Padmanabhan |
| المصدر: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-13 (2019) |
| بيانات النشر: | Nature Publishing Group UK, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Cytochrome, Protein subunit, lcsh:Medicine, Oxidative phosphorylation, Reductase, Protein function predictions, Molecular Dynamics Simulation, Article, 03 medical and health sciences, Electron Transport Complex III, Mice, 0302 clinical medicine, Cardiotoxin, Muscular Diseases, medicine, Animals, Muscular dystrophy, lcsh:Science, Multidisciplinary, biology, Chemistry, lcsh:R, Tryptophan, Cytochromes c, medicine.disease, 030104 developmental biology, Biochemistry, Coenzyme Q – cytochrome c reductase, biology.protein, Protein structure predictions, lcsh:Q, Intermembrane space, Oxidation-Reduction, 030217 neurology & neurosurgery |
| الوصف: | Muscle diseases display mitochondrial dysfunction and oxidative damage. Our previous study in a cardiotoxin model of myodegeneration correlated muscle damage with mitochondrial dysfunction, which in turn entailed altered mitochondrial proteome and oxidative damage of mitochondrial proteins. Proteomic identification of oxidized proteins in muscle biopsies from muscular dystrophy patients and cardiotoxin model revealed specific mitochondrial proteins to be targeted for oxidation. These included respiratory complexes which displayed oxidative modification of Trp residues in different subunits. Among these, Ubiquinol-Cytochrome C Reductase Core protein 1 (UQCRC1), a subunit of Ubiquinol-Cytochrome C Reductase Complex or Cytochrome b-c1 Complex or Respiratory Complex III displayed oxidation of Trp395, which could be correlated with the lowered activity of Complex III. We hypothesized that Trp395 oxidation might contribute to altered local conformation and overall structure of Complex III, thereby potentially leading to altered protein activity. To address this, we performed molecular dynamics simulation of Complex III (oxidized at Trp395 of UQCRC1 vs. non-oxidized control). Molecular dynamic simulation analyses revealed local structural changes in the Trp395 site. Intriguingly, oxidized Trp395 contributed to decreased plasticity of Complex III due to significant cross-talk among the subunits in the matrix-facing region and subunits in the intermembrane space, thereby leading to impaired electron flow from cytochrome C. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f32e7f14499c670fa3e9ee84ae7eaa12 http://europepmc.org/articles/PMC6650490 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....f32e7f14499c670fa3e9ee84ae7eaa12 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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