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| | ==Crystal Structure of the Cataract-Causing P23T gamma D-Crystallin Mutant== | | ==Crystal Structure of the Cataract-Causing P23T gamma D-Crystallin Mutant== |
| - | <StructureSection load='4jgf' size='340' side='right' caption='[[4jgf]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='4jgf' size='340' side='right'caption='[[4jgf]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4jgf]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JGF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JGF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4jgf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JGF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JGF FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CRYGD, CRYG4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4jgf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jgf OCA], [http://pdbe.org/4jgf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jgf RCSB], [http://www.ebi.ac.uk/pdbsum/4jgf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jgf ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4jgf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jgf OCA], [https://pdbe.org/4jgf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jgf RCSB], [https://www.ebi.ac.uk/pdbsum/4jgf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jgf ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/CRGD_HUMAN CRGD_HUMAN]] Defects in CRYGD are a cause of cataract autosomal dominant (ADC) [MIM:[http://omim.org/entry/604219 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.<ref>PMID:9927684</ref> <ref>PMID:10688888</ref> <ref>PMID:21031598</ref> Defects in CRYGD are the cause of cataract congenital non-nuclear polymorphic autosomal dominant (CCP) [MIM:[http://omim.org/entry/601286 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.<ref>PMID:16943771</ref> <ref>PMID:17564961</ref> Defects in CRYGD are the cause of cataract congenital cerulean type 3 (CCA3) [MIM:[http://omim.org/entry/608983 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:[http://omim.org/entry/115700 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.<ref>PMID:10521291</ref> | + | [https://www.uniprot.org/uniprot/CRGD_HUMAN CRGD_HUMAN] Defects in CRYGD are a cause of cataract autosomal dominant (ADC) [MIM:[https://omim.org/entry/604219 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.<ref>PMID:9927684</ref> <ref>PMID:10688888</ref> <ref>PMID:21031598</ref> Defects in CRYGD are the cause of cataract congenital non-nuclear polymorphic autosomal dominant (CCP) [MIM:[https://omim.org/entry/601286 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.<ref>PMID:16943771</ref> <ref>PMID:17564961</ref> Defects in CRYGD are the cause of cataract congenital cerulean type 3 (CCA3) [MIM:[https://omim.org/entry/608983 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:[https://omim.org/entry/115700 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.<ref>PMID:10521291</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CRGD_HUMAN CRGD_HUMAN]] Crystallins are the dominant structural components of the vertebrate eye lens. | + | [https://www.uniprot.org/uniprot/CRGD_HUMAN CRGD_HUMAN] Crystallins are the dominant structural components of the vertebrate eye lens. |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Up 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.
| + | |
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| - | 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<ref>PMID:23670788</ref>
| + | ==See Also== |
| - | | + | *[[Crystallin 3D structures|Crystallin 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 4jgf" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Gronenborn, A M]] | + | [[Category: Large Structures]] |
| - | [[Category: Ji, F L]] | + | [[Category: Gronenborn AM]] |
| - | [[Category: Jung, J W]] | + | [[Category: Ji FL]] |
| - | [[Category: Koharudin, L M]] | + | [[Category: Jung JW]] |
| - | [[Category: Structural protein]] | + | [[Category: Koharudin LM]] |
| 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.
See Also
References
- ↑ Stephan DA, Gillanders E, Vanderveen D, Freas-Lutz D, Wistow G, Baxevanis AD, Robbins CM, VanAuken A, Quesenberry MI, Bailey-Wilson J, Juo SH, Trent JM, Smith L, Brownstein MJ. Progressive juvenile-onset punctate cataracts caused by mutation of the gammaD-crystallin gene. Proc Natl Acad Sci U S A. 1999 Feb 2;96(3):1008-12. PMID:9927684
- ↑ Pande A, Pande J, Asherie N, Lomakin A, Ogun O, King JA, Lubsen NH, Walton D, Benedek GB. Molecular basis of a progressive juvenile-onset hereditary cataract. Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):1993-8. PMID:10688888 doi:10.1073/pnas.040554397
- ↑ Wang B, Yu C, Xi YB, Cai HC, Wang J, Zhou S, Zhou S, Wu Y, Yan YB, Ma X, Xie L. A novel CRYGD mutation (p.Trp43Arg) causing autosomal dominant congenital cataract in a Chinese family. Hum Mutat. 2011 Jan;32(1):E1939-47. doi: 10.1002/humu.21386. PMID:21031598 doi:10.1002/humu.21386
- ↑ Messina-Baas OM, Gonzalez-Huerta LM, Cuevas-Covarrubias SA. Two affected siblings with nuclear cataract associated with a novel missense mutation in the CRYGD gene. Mol Vis. 2006 Aug 24;12:995-1000. PMID:16943771
- ↑ Plotnikova OV, Kondrashov FA, Vlasov PK, Grigorenko AP, Ginter EK, Rogaev EI. Conversion and compensatory evolution of the gamma-crystallin genes and identification of a cataractogenic mutation that reverses the sequence of the human CRYGD gene to an ancestral state. Am J Hum Genet. 2007 Jul;81(1):32-43. Epub 2007 May 16. PMID:17564961 doi:S0002-9297(07)62814-6
- ↑ Heon E, Priston M, Schorderet DF, Billingsley GD, Girard PO, Lubsen N, Munier FL. The gamma-crystallins and human cataracts: a puzzle made clearer. Am J Hum Genet. 1999 Nov;65(5):1261-7. PMID:10521291 doi:10.1086/302619
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