4jgf | pdb_00004jgf
Crystal Structure of the Cataract-Causing P23T gamma D-Crystallin Mutant
Structural highlights
Disease[CRGD_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] Function[CRGD_HUMAN] Crystallins are the dominant structural components of the vertebrate eye lens. Publication Abstract from PubMedUp to now, efforts to crystallize the cataract-associated P23T mutant of human gammaD-crystallin have not been successful. Therefore, insights into the light scattering mechanism of this mutant have been exclusively obtained from solution work. Here we present the first crystal structure of the P23T mutant at 2.5 A resolution. The protein exhibits essentially the same overall structure as seen for the wild-type protein. Based on our structural data, we confirm that no major conformational changes are caused by the mutation, and that solution phase properties of the mutant appear exclusively associated with cataract formation. Proteins 2013. (c) 2013 Wiley Periodicals, Inc. Crystal structure of the cataract-causing P23T gammaD-crystallin mutant.,Ji F, Koharudin LM, Jung J, Gronenborn AM Proteins. 2013 May 13. doi: 10.1002/prot.24321. PMID:23670788[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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