8BD0

Human Gamma-D crystallin R36S mutant with DTT-Cystein Protein modification

8BD0 の概要

• エントリーDOI: 10.2210/pdb8bd0/pdb
• 分子名称: Human Gamma-D Crystallin R36S, 2,3-DIHYDROXY-1,4-DITHIOBUTANE (3 entities in total)
• 機能のキーワード: chemical modification, oxidisation, eye lens protein, structural protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 41310.20

構造登録者

Yorke, B.A.,Hill, J.A. (登録日: 2022-10-17, 公開日: 2023-11-01, 最終更新日: 2024-10-16)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2 Å)