Functionally active cross-linked protein oligomers formed by homocysteine thiolactone
Abstract Deposition of high-order protein oligomers is a common hallmark of a large number of human diseases and therefore, has been of immense medical interest. From the past several decades, efforts are being made to characterize protein oligomers and explore how they are linked with the disease p...
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| Format: | Article |
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Nature Portfolio
2023-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-32694-2 |
| _version_ | 1827970484367523840 |
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| author | Kritika Kumari Gurumayum Suraj Sharma Akshita Gupta Khuraijam Surjalal Singh Laishram Rajendrakumar Singh |
| author_facet | Kritika Kumari Gurumayum Suraj Sharma Akshita Gupta Khuraijam Surjalal Singh Laishram Rajendrakumar Singh |
| author_sort | Kritika Kumari |
| collection | DOAJ |
| description | Abstract Deposition of high-order protein oligomers is a common hallmark of a large number of human diseases and therefore, has been of immense medical interest. From the past several decades, efforts are being made to characterize protein oligomers and explore how they are linked with the disease pathologies. In general, oligomers are non-functional, rather cytotoxic in nature while the functional (non-cytotoxic) oligomers are quite rare. In the present study, we identified new protein oligomers of Ribonuclease-A and Lysozyme that contain functionally active fractions. These functional oligomers are disulfide cross-linked, native-like, and obtained as a result of the covalent modification of the proteins by the toxic metabolite, homocysteine thiolactone accumulated under hyperhomocysteinemia (a condition responsible for cardiovascular complications including atherosclerosis). These results have been obtained from the extensive analysis of the nature of oligomers, functional status, and structural integrity of the proteins using orthogonal techniques. The study implicates the existence of such oligomers as protein sinks that may sequester toxic homocysteines in humans. |
| first_indexed | 2024-04-09T18:54:34Z |
| format | Article |
| id | doaj.art-1698fd988c6447be9841e9ad636c62b1 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T18:54:34Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-1698fd988c6447be9841e9ad636c62b12023-04-09T11:15:29ZengNature PortfolioScientific Reports2045-23222023-04-0113111210.1038/s41598-023-32694-2Functionally active cross-linked protein oligomers formed by homocysteine thiolactoneKritika Kumari0Gurumayum Suraj Sharma1Akshita Gupta2Khuraijam Surjalal Singh3Laishram Rajendrakumar Singh4Dr. B. R. Ambedkar Center for Biomedical Research, University of DelhiDepartment of Botany, Bhaskaracharya College of Applied Sciences, University of DelhiDr. B. R. Ambedkar Center for Biomedical Research, University of DelhiDr. B. R. Ambedkar Center for Biomedical Research, University of DelhiDr. B. R. Ambedkar Center for Biomedical Research, University of DelhiAbstract Deposition of high-order protein oligomers is a common hallmark of a large number of human diseases and therefore, has been of immense medical interest. From the past several decades, efforts are being made to characterize protein oligomers and explore how they are linked with the disease pathologies. In general, oligomers are non-functional, rather cytotoxic in nature while the functional (non-cytotoxic) oligomers are quite rare. In the present study, we identified new protein oligomers of Ribonuclease-A and Lysozyme that contain functionally active fractions. These functional oligomers are disulfide cross-linked, native-like, and obtained as a result of the covalent modification of the proteins by the toxic metabolite, homocysteine thiolactone accumulated under hyperhomocysteinemia (a condition responsible for cardiovascular complications including atherosclerosis). These results have been obtained from the extensive analysis of the nature of oligomers, functional status, and structural integrity of the proteins using orthogonal techniques. The study implicates the existence of such oligomers as protein sinks that may sequester toxic homocysteines in humans.https://doi.org/10.1038/s41598-023-32694-2 |
| spellingShingle | Kritika Kumari Gurumayum Suraj Sharma Akshita Gupta Khuraijam Surjalal Singh Laishram Rajendrakumar Singh Functionally active cross-linked protein oligomers formed by homocysteine thiolactone Scientific Reports |
| title | Functionally active cross-linked protein oligomers formed by homocysteine thiolactone |
| title_full | Functionally active cross-linked protein oligomers formed by homocysteine thiolactone |
| title_fullStr | Functionally active cross-linked protein oligomers formed by homocysteine thiolactone |
| title_full_unstemmed | Functionally active cross-linked protein oligomers formed by homocysteine thiolactone |
| title_short | Functionally active cross-linked protein oligomers formed by homocysteine thiolactone |
| title_sort | functionally active cross linked protein oligomers formed by homocysteine thiolactone |
| url | https://doi.org/10.1038/s41598-023-32694-2 |
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