An ultraviolet-driven rescue pathway for oxidative stress to eye lens protein human gamma-D crystallin.
Journal
Communications chemistry
ISSN: 2399-3669
Titre abrégé: Commun Chem
Pays: England
ID NLM: 101725670
Informations de publication
Date de publication:
10 Apr 2024
10 Apr 2024
Historique:
received:
04
10
2023
accepted:
27
03
2024
medline:
11
4
2024
pubmed:
11
4
2024
entrez:
10
4
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38600176
doi: 10.1038/s42004-024-01163-w
pii: 10.1038/s42004-024-01163-w
doi:
Types de publication
Journal Article
Langues
eng
Pagination
81Subventions
Organisme : Academy of Medical Sciences
ID : SBF006044
Pays : United Kingdom
Informations de copyright
© 2024. The Author(s).
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