Hill, J.A. orcid.org/0000-0002-9984-3387, Nyathi, Y., Horrell, S. orcid.org/0000-0001-6355-8640 et al. (7 more authors) (2024) An ultraviolet-driven rescue pathway for oxidative stress to eye lens protein human gamma-D crystallin. Communications Chemistry, 7. 81.
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2024. This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemistry (Leeds) > Physical Chemistry (Leeds) |
Funding Information: | Funder Grant number Academy of Medical Sciences SBF006\1044 |
Depositing User: | Symplectic Publications |
Date Deposited: | 12 Apr 2024 13:04 |
Last Modified: | 12 Apr 2024 13:04 |
Status: | Published |
Publisher: | Nature Research |
Identification Number: | 10.1038/s42004-024-01163-w |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:211410 |