6FD8

Gamma-s crystallin dimer

Summary for 6FD8

• Entry DOI: 10.2210/pdb6fd8/pdb
• Descriptor: Beta-crystallin S (2 entities in total)
• Functional Keywords: crystallin, eye lens, vision, cataract., structural protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 42067.55

Authors

Mabbitt, P.D.,Thorn, D.C.,Jackson, C.J.,Carver, J.A. (deposition date: 2017-12-22, release date: 2018-12-26, Last modification date: 2024-11-06)

Primary citation

Thorn, D.C.,Grosas, A.B.,Mabbitt, P.D.,Ray, N.J.,Jackson, C.J.,Carver, J.A.
The Structure and Stability of the Disulfide-Linked gamma S-Crystallin Dimer Provide Insight into Oxidation Products Associated with Lens Cataract Formation.
J. Mol. Biol., 431:483-497, 2019

PubMed Abstract: The reducing environment in the eye lens diminishes with age, leading to significant oxidative stress. Oxidation of lens crystallin proteins is the major contributor to their destabilization and deleterious aggregation that scatters visible light, obscures vision, and ultimately leads to cataract. However, the molecular basis for oxidation-induced aggregation is unknown. Using X-ray crystallography and small-angle X-ray scattering, we describe the structure of a disulfide-linked dimer of human γS-crystallin that was obtained via oxidation of C24. The γS-crystallin dimer is stable at glutathione concentrations comparable to those in aged and cataractous lenses. Moreover, dimerization of γS-crystallin significantly increases the protein's propensity to form large insoluble aggregates owing to non-cooperative domain unfolding, as is observed in crystallin variants associated with early-onset cataract. These findings provide insight into how oxidative modification of crystallins contributes to cataract and imply that early-onset and age-related forms of the disease share comparable development pathways.

PubMed: 30552875
DOI: 10.1016/j.jmb.2018.12.005

Experimental method

X-RAY DIFFRACTION (2.1 Å)