An ultraviolet-driven rescue pathway for oxidative stress to eye lens protein human gamma-D crystallin

DOI: 10.1038/s42004-024-01163-w

Authors: Jake A. Hill (University of Bradford; University of Leeds) , Yvonne Nyathi (University of Leeds) , Sam Horrell (Diamond Light Source) , David Von Stetten (European Molecular Biology Laboratory) , Danny Axford (Diamond Light Source) , Robin L. Owen (Diamond Light Source) , Godfrey S. Beddard (University of Leeds; University of Edinburgh) , Arwen R. Pearson (HARBOR, Institute for Nanostructure and Solid State Physics) , Helen M. Ginn (HARBOR, Institute for Nanostructure and Solid State Physics; CFEL, Deutsches Elektronen-Synchrotron DESY) , Briony Yorke (University of Leeds)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Communications Chemistry , VOL 7

State: Published (Approved)
Published: April 2024
Diamond Proposal Number(s): 27314

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.

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: I24-Microfocus Macromolecular Crystallography

Other Facilities: P14 at PETRA III at DESY

Added On: 15/04/2024 09:56

Documents:
s42004-024-01163-w.pdf

Discipline Tags:

Health & Wellbeing Biochemistry Chemistry Structural biology Ophthalmology Life Sciences & Biotech

Technical Tags:

Diffraction Serial Synchrotron Crystallography (SSX)