Academic Journal
Evolution of an Iron-Detoxifying Protein: Eukaryotic and Rickettsia Frataxins Contain a Conserved Site Which Is Not Present in Their Bacterial Homologues
| العنوان: | Evolution of an Iron-Detoxifying Protein: Eukaryotic and Rickettsia Frataxins Contain a Conserved Site Which Is Not Present in Their Bacterial Homologues |
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| المؤلفون: | Alves, Rui, Pazos Gil, Maria, Medina Carbonero, Marta, Sanz Alcázar, Arabela, Delaspre, Fabien, Tamarit Sumalla, Jordi |
| بيانات النشر: | MDPI |
| سنة النشر: | 2022 |
| المجموعة: | Universitat de Lleida: Repositori Obert UdL |
| مصطلحات موضوعية: | Iron, Friedreich’s ataxia, Mitochondria, Protein evolution |
| الوصف: | Friedreich’s ataxia is a neurodegenerative disease caused by mutations in the frataxin gene. Frataxin homologues, including bacterial CyaY proteins, can be found in most species and play a fundamental role in mitochondrial iron homeostasis, either promoting iron assembly into metaloproteins or contributing to iron detoxification. While several lines of evidence suggest that eukaryotic frataxins are more effective than bacterial ones in iron detoxification, the residues involved in this gain of function are unknown. In this work, we analyze conservation of amino acid sequence and protein structure among frataxins and CyaY proteins to identify four highly conserved residue clusters and group them into potential functional clusters. Clusters 1, 2, and 4 are present in eukaryotic frataxins and bacterial CyaY proteins. Cluster 3, containing two serines, a tyrosine, and a glutamate, is only present in eukaryotic frataxins and on CyaY proteins from the Rickettsia genus. Residues from cluster 3 are blocking a small cavity of about 40 Å present in E. coli’s CyaY. The function of this cluster is unknown, but we hypothesize that its tyrosine may contribute to prevent formation of reactive oxygen species during iron detoxification. This cluster provides an example of gain of function during evolution in a protein involved in iron homeostasis, as our results suggests that Cluster 3 was present in the endosymbiont ancestor of mitochondria and was conserved in eukaryotic frataxins. ; This research was funded by Ministerio de Ciencia e Innovación (Spain), grant number PID2020-118296RB-I00 |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1422-0067 |
| Relation: | info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-118296RB-I00/ES/MECANISMOS DE DISFUNCION MITOCONDRIAL Y NUEVAS ESTRATEGIAS TERAPEUTICAS EN MODELOS CELULARES Y ANIMALES DE ATAXIA DE FRIEDREICH /; Reproducció del document publicat a: https://doi.org/10.3390/ijms232113151issn; International Journal of Molecular Sciences, 2022, vol. 23, núm. 21; https://doi.org/10.3390/ijms232113151issn; 033031; http://hdl.handle.net/10459.1/84485 |
| DOI: | 10.3390/ijms232113151issn |
| الاتاحة: | http://hdl.handle.net/10459.1/84485 https://doi.org/10.3390/ijms232113151issn |
| Rights: | cc-by (c) authors, 2022 ; info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.F06B5FF7 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14220067 |
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| DOI: | 10.3390/ijms232113151issn |