An ultraviolet-driven rescue pathway for oxidative stress to eye lens protein human gamma-D crystallin
Abstract Human gamma-D crystallin (HGD) is a major constituent of the eye lens. Aggregation of HGD contributes to cataract formation, the leading cause of blindness worldwide. It is unique in its longevity, maintaining its folded and soluble state for 50-60 years. One outstanding question is the str...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-04-01
|
| Series: | Communications Chemistry |
| Online Access: | https://doi.org/10.1038/s42004-024-01163-w |
| _version_ | 1797209493550923776 |
|---|---|
| author | Jake A. Hill Yvonne Nyathi Sam Horrell David von Stetten Danny Axford Robin L. Owen Godfrey S. Beddard Arwen R. Pearson Helen M. Ginn Briony A. Yorke |
| author_facet | Jake A. Hill Yvonne Nyathi Sam Horrell David von Stetten Danny Axford Robin L. Owen Godfrey S. Beddard Arwen R. Pearson Helen M. Ginn Briony A. Yorke |
| author_sort | Jake A. Hill |
| collection | DOAJ |
| description | Abstract Human gamma-D crystallin (HGD) is a major constituent of the eye lens. Aggregation of HGD contributes to cataract formation, the leading cause of blindness worldwide. It is unique in its longevity, maintaining its folded and soluble state for 50-60 years. One outstanding question is the structural basis of this longevity despite oxidative aging and environmental stressors including ultraviolet radiation (UV). Here we present crystallographic structures evidencing a UV-induced crystallin redox switch mechanism. The room-temperature serial synchrotron crystallographic (SSX) structure of freshly prepared crystallin mutant (R36S) shows no post-translational modifications. After aging for nine months in the absence of light, a thiol-adduct (dithiothreitol) modifying surface cysteines is observed by low-dose SSX. This is shown to be UV-labile in an acutely light-exposed structure. This suggests a mechanism by which a major source of crystallin damage, UV, may also act as a rescuing factor in a finely balanced redox system. |
| first_indexed | 2024-04-24T09:55:35Z |
| format | Article |
| id | doaj.art-a7a4539ed52244a9845ffd7debe82e95 |
| institution | Directory Open Access Journal |
| issn | 2399-3669 |
| language | English |
| last_indexed | 2024-04-24T09:55:35Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Chemistry |
| spelling | doaj.art-a7a4539ed52244a9845ffd7debe82e952024-04-14T11:09:44ZengNature PortfolioCommunications Chemistry2399-36692024-04-01711810.1038/s42004-024-01163-wAn ultraviolet-driven rescue pathway for oxidative stress to eye lens protein human gamma-D crystallinJake A. Hill0Yvonne Nyathi1Sam Horrell2David von Stetten3Danny Axford4Robin L. Owen5Godfrey S. Beddard6Arwen R. Pearson7Helen M. Ginn8Briony A. Yorke9School of Chemistry and Biosciences, University of BradfordFaculty of Biological Sciences, University of LeedsDiamond Light Source Ltd, Harwell Science and Innovation CampusEuropean Molecular Biology LaboratoryDiamond Light Source Ltd, Harwell Science and Innovation CampusDiamond Light Source Ltd, Harwell Science and Innovation CampusSchool of Chemistry, University of LeedsHARBOR, Institute for Nanostructure and Solid State PhysicsHARBOR, Institute for Nanostructure and Solid State PhysicsSchool of Chemistry, University of LeedsAbstract Human gamma-D crystallin (HGD) is a major constituent of the eye lens. Aggregation of HGD contributes to cataract formation, the leading cause of blindness worldwide. It is unique in its longevity, maintaining its folded and soluble state for 50-60 years. One outstanding question is the structural basis of this longevity despite oxidative aging and environmental stressors including ultraviolet radiation (UV). Here we present crystallographic structures evidencing a UV-induced crystallin redox switch mechanism. The room-temperature serial synchrotron crystallographic (SSX) structure of freshly prepared crystallin mutant (R36S) shows no post-translational modifications. After aging for nine months in the absence of light, a thiol-adduct (dithiothreitol) modifying surface cysteines is observed by low-dose SSX. This is shown to be UV-labile in an acutely light-exposed structure. This suggests a mechanism by which a major source of crystallin damage, UV, may also act as a rescuing factor in a finely balanced redox system.https://doi.org/10.1038/s42004-024-01163-w |
| spellingShingle | Jake A. Hill Yvonne Nyathi Sam Horrell David von Stetten Danny Axford Robin L. Owen Godfrey S. Beddard Arwen R. Pearson Helen M. Ginn Briony A. Yorke An ultraviolet-driven rescue pathway for oxidative stress to eye lens protein human gamma-D crystallin Communications Chemistry |
| title | An ultraviolet-driven rescue pathway for oxidative stress to eye lens protein human gamma-D crystallin |
| title_full | An ultraviolet-driven rescue pathway for oxidative stress to eye lens protein human gamma-D crystallin |
| title_fullStr | An ultraviolet-driven rescue pathway for oxidative stress to eye lens protein human gamma-D crystallin |
| title_full_unstemmed | An ultraviolet-driven rescue pathway for oxidative stress to eye lens protein human gamma-D crystallin |
| title_short | An ultraviolet-driven rescue pathway for oxidative stress to eye lens protein human gamma-D crystallin |
| title_sort | ultraviolet driven rescue pathway for oxidative stress to eye lens protein human gamma d crystallin |
| url | https://doi.org/10.1038/s42004-024-01163-w |
| work_keys_str_mv | AT jakeahill anultravioletdrivenrescuepathwayforoxidativestresstoeyelensproteinhumangammadcrystallin AT yvonnenyathi anultravioletdrivenrescuepathwayforoxidativestresstoeyelensproteinhumangammadcrystallin AT samhorrell anultravioletdrivenrescuepathwayforoxidativestresstoeyelensproteinhumangammadcrystallin AT davidvonstetten anultravioletdrivenrescuepathwayforoxidativestresstoeyelensproteinhumangammadcrystallin AT dannyaxford anultravioletdrivenrescuepathwayforoxidativestresstoeyelensproteinhumangammadcrystallin AT robinlowen anultravioletdrivenrescuepathwayforoxidativestresstoeyelensproteinhumangammadcrystallin AT godfreysbeddard anultravioletdrivenrescuepathwayforoxidativestresstoeyelensproteinhumangammadcrystallin AT arwenrpearson anultravioletdrivenrescuepathwayforoxidativestresstoeyelensproteinhumangammadcrystallin AT helenmginn anultravioletdrivenrescuepathwayforoxidativestresstoeyelensproteinhumangammadcrystallin AT brionyayorke anultravioletdrivenrescuepathwayforoxidativestresstoeyelensproteinhumangammadcrystallin AT jakeahill ultravioletdrivenrescuepathwayforoxidativestresstoeyelensproteinhumangammadcrystallin AT yvonnenyathi ultravioletdrivenrescuepathwayforoxidativestresstoeyelensproteinhumangammadcrystallin AT samhorrell ultravioletdrivenrescuepathwayforoxidativestresstoeyelensproteinhumangammadcrystallin AT davidvonstetten ultravioletdrivenrescuepathwayforoxidativestresstoeyelensproteinhumangammadcrystallin AT dannyaxford ultravioletdrivenrescuepathwayforoxidativestresstoeyelensproteinhumangammadcrystallin AT robinlowen ultravioletdrivenrescuepathwayforoxidativestresstoeyelensproteinhumangammadcrystallin AT godfreysbeddard ultravioletdrivenrescuepathwayforoxidativestresstoeyelensproteinhumangammadcrystallin AT arwenrpearson ultravioletdrivenrescuepathwayforoxidativestresstoeyelensproteinhumangammadcrystallin AT helenmginn ultravioletdrivenrescuepathwayforoxidativestresstoeyelensproteinhumangammadcrystallin AT brionyayorke ultravioletdrivenrescuepathwayforoxidativestresstoeyelensproteinhumangammadcrystallin |