8BPI

Human Gamma-D crystallin R36S mutant after UV illumination

This is a non-PDB format compatible entry.

Summary for 8BPI

• Entry DOI: 10.2210/pdb8bpi/pdb
• Descriptor: Gamma-crystallin D (3 entities in total)
• Functional Keywords: uv exposure, oxidisation, eye lens protein, structural protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 43644.48

Authors

Yorke, B.A.,Hill, J.A. (deposition date: 2022-11-16, release date: 2023-11-29, Last modification date: 2024-08-14)

Primary citation

Hill, J.A.,Nyathi, Y.,Horrell, S.,von Stetten, D.,Axford, D.,Owen, R.L.,Beddard, G.S.,Pearson, A.R.,Ginn, H.M.,Yorke, B.A.
An ultraviolet-driven rescue pathway for oxidative stress to eye lens protein human gamma-D crystallin.
Commun Chem, 7:81-81, 2024

PubMed 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.

PubMed: 38600176
DOI: 10.1038/s42004-024-01163-w

Experimental method

X-RAY DIFFRACTION (2 Å)