pH induced conformational alteration in human peroxiredoxin 6 might be responsible for its resistance against lysosomal pH or high temperature
Abstract Peroxiredoxin 6 (Prdx6), the ubiquitously expressed enzyme belonging to the family of peroxidases, namely, peroxiredoxins, exhibits a unique feature of functional compartmentalization within cells. Whereas, the enzyme localized in cytosol shows glutathione peroxidase activity, its lysosomal...
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doaj-e31d544a68084e5db1f7144c130cd78b2021-05-09T11:33:12ZengNature Publishing GroupScientific Reports2045-23222021-05-0111111010.1038/s41598-021-89093-8pH induced conformational alteration in human peroxiredoxin 6 might be responsible for its resistance against lysosomal pH or high temperatureRimpy Kaur Chowhan0Sunaina Hotumalani1Hamidur Rahaman2Laishram Rajendrakumar Singh3Dr. B. R. Ambedkar Center for Biomedical Research, University of DelhiDr. B. R. Ambedkar Center for Biomedical Research, University of DelhiDepartment of Biotechnology, Manipur UniversityDr. B. R. Ambedkar Center for Biomedical Research, University of DelhiAbstract Peroxiredoxin 6 (Prdx6), the ubiquitously expressed enzyme belonging to the family of peroxidases, namely, peroxiredoxins, exhibits a unique feature of functional compartmentalization within cells. Whereas, the enzyme localized in cytosol shows glutathione peroxidase activity, its lysosomal counterpart performs calcium independent phospholipase A2 (aiPLA2) activity. Like any true moonlighting protein, these two activities of Prdx6 are mutually exclusive of each other as a function of the pH of the cellular compartments. Differential substrate preference at different pH (i.e. peroxidised phospholipids at neutral pH and reduced phospholipids at acidic pH) is considered to be the reason for this behavior. To gain insight into the pH-induced structural–functional interplay we have systematically evaluated conformational variations, thermodynamic stability of the protein and quaternary state of the conformers at both pH 7.0 and 4.0. Our findings suggest that change in pH allows alterations in native states of Prdx6 at pH 7.0 and 4.0 such that the changes make the protein resistant to thermal denaturation at low pH.https://doi.org/10.1038/s41598-021-89093-8 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rimpy Kaur Chowhan Sunaina Hotumalani Hamidur Rahaman Laishram Rajendrakumar Singh |
spellingShingle |
Rimpy Kaur Chowhan Sunaina Hotumalani Hamidur Rahaman Laishram Rajendrakumar Singh pH induced conformational alteration in human peroxiredoxin 6 might be responsible for its resistance against lysosomal pH or high temperature Scientific Reports |
author_facet |
Rimpy Kaur Chowhan Sunaina Hotumalani Hamidur Rahaman Laishram Rajendrakumar Singh |
author_sort |
Rimpy Kaur Chowhan |
title |
pH induced conformational alteration in human peroxiredoxin 6 might be responsible for its resistance against lysosomal pH or high temperature |
title_short |
pH induced conformational alteration in human peroxiredoxin 6 might be responsible for its resistance against lysosomal pH or high temperature |
title_full |
pH induced conformational alteration in human peroxiredoxin 6 might be responsible for its resistance against lysosomal pH or high temperature |
title_fullStr |
pH induced conformational alteration in human peroxiredoxin 6 might be responsible for its resistance against lysosomal pH or high temperature |
title_full_unstemmed |
pH induced conformational alteration in human peroxiredoxin 6 might be responsible for its resistance against lysosomal pH or high temperature |
title_sort |
ph induced conformational alteration in human peroxiredoxin 6 might be responsible for its resistance against lysosomal ph or high temperature |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-05-01 |
description |
Abstract Peroxiredoxin 6 (Prdx6), the ubiquitously expressed enzyme belonging to the family of peroxidases, namely, peroxiredoxins, exhibits a unique feature of functional compartmentalization within cells. Whereas, the enzyme localized in cytosol shows glutathione peroxidase activity, its lysosomal counterpart performs calcium independent phospholipase A2 (aiPLA2) activity. Like any true moonlighting protein, these two activities of Prdx6 are mutually exclusive of each other as a function of the pH of the cellular compartments. Differential substrate preference at different pH (i.e. peroxidised phospholipids at neutral pH and reduced phospholipids at acidic pH) is considered to be the reason for this behavior. To gain insight into the pH-induced structural–functional interplay we have systematically evaluated conformational variations, thermodynamic stability of the protein and quaternary state of the conformers at both pH 7.0 and 4.0. Our findings suggest that change in pH allows alterations in native states of Prdx6 at pH 7.0 and 4.0 such that the changes make the protein resistant to thermal denaturation at low pH. |
url |
https://doi.org/10.1038/s41598-021-89093-8 |
work_keys_str_mv |
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