8bpi
From Proteopedia
Human Gamma-D crystallin R36S mutant after UV illumination
Structural highlights
DiseaseCRGD_HUMAN Defects in CRYGD are a cause of cataract autosomal dominant (ADC) [MIM:604219. Cataract is an opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. Cataract is the most common treatable cause of visual disability in childhood.[1] [2] [3] Defects in CRYGD are the cause of cataract congenital non-nuclear polymorphic autosomal dominant (CCP) [MIM:601286; also known as polymorphic congenital cataract. A congenital cataract characterized by a non-progressive phenotype and partial opacity that has a variable location between the fetal nucleus of the lens and the equator. The fetal nucleus is normal. The opacities are irregular and look similar to a bunch of grapes and may be present simultaneously in different lens layers.[4] [5] Defects in CRYGD are the cause of cataract congenital cerulean type 3 (CCA3) [MIM:608983; also known as congenital cataract blue dot type 3. A cerulean form of autosomal dominant congenital cataract. Cerulean cataract is characterized by peripheral bluish and white opacifications organized in concentric layers with occasional central lesions arranged radially. The opacities are observed in the superficial layers of the fetal nucleus as well as the adult nucleus of the lens. Involvement is usually bilateral. Visual acuity is only mildly reduced in childhood. In adulthood, the opacifications may progress, making lens extraction necessary. Histologically the lesions are described as fusiform cavities between lens fibers which contain a deeply staining granular material. Although the lesions may take on various colors, a dull blue is the most common appearance and is responsible for the designation cerulean cataract. Defects in CRYGD are the cause of cataract crystalline aculeiform (CACA) [MIM:115700. A congenital crystalline cataract characterized by fiberglass-like or needle-like crystals projecting in different directions, through or close to the axial region of the lens. The opacity causes a variable degree of vision loss.[6] FunctionCRGD_HUMAN Crystallins are the dominant structural components of the vertebrate eye lens. Publication Abstract from PubMedHuman 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. An ultraviolet-driven rescue pathway for oxidative stress to eye lens protein human gamma-D crystallin.,Hill JA, Nyathi Y, Horrell S, von Stetten D, Axford D, Owen RL, Beddard GS, Pearson AR, Ginn HM, Yorke BA Commun Chem. 2024 Apr 10;7(1):81. doi: 10.1038/s42004-024-01163-w. PMID:38600176[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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