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6eta

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Crystal Structure of Human Gamma-D crystallin Mutant P23T+R36S at Room Temperature

Structural highlights

6eta is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	CRYGD, CRYG4 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 PubMed

Protein crystal production is a major bottleneck in the structural characterization of proteins. To advance beyond large-scale screening, rational strategies for protein crystallization are crucial. Understanding how chemical anisotropy (or patchiness) of the protein surface, due to the variety of amino-acid side chains in contact with solvent, contributes to protein-protein contact formation in the crystal lattice is a major obstacle to predicting and optimizing crystallization. The relative scarcity of sophisticated theoretical models that include sufficient detail to link collective behavior, captured in protein phase diagrams, and molecular-level details, determined from high-resolution structural information, is a further barrier. Here, we present two crystal structures for the P23T + R36S mutant of gammaD-crystallin, each with opposite solubility behavior: one melts when heated, the other when cooled. When combined with the protein phase diagram and a tailored patchy particle model, we show that a single temperature-dependent interaction is sufficient to stabilize the inverted solubility crystal. This contact, at the P23T substitution site, relates to a genetic cataract and reveals at a molecular level the origin of the lowered and retrograde solubility of the protein. Our results show that the approach employed here may present a productive strategy for the rationalization of protein crystallization.

Temperature-Dependent Interactions Explain Normal and Inverted Solubility in a gammaD-Crystallin Mutant.,Khan AR, James S, Quinn MK, Altan I, Charbonneau P, McManus JJ Biophys J. 2019 Sep 3;117(5):930-937. doi: 10.1016/j.bpj.2019.07.019. Epub 2019, Jul 19. PMID:31422822^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Khan AR, James S, Quinn MK, Altan I, Charbonneau P, McManus JJ. Temperature-Dependent Interactions Explain Normal and Inverted Solubility in a gammaD-Crystallin Mutant. Biophys J. 2019 Sep 3;117(5):930-937. doi: 10.1016/j.bpj.2019.07.019. Epub 2019, Jul 19. PMID:31422822 doi:http://dx.doi.org/10.1016/j.bpj.2019.07.019

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6eta"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Human Gamma-D crystallin Mutant P23T+R36S at Room Temperature==
-<StructureSection load='6eta' size='340' side='right' caption='[[6eta]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+<StructureSection load='6eta' size='340' side='right'caption='[[6eta]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6eta]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ETA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ETA FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6eta]] 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=6ETA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ETA FirstGlance]. <br>
-</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=6eta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eta OCA], [http://pdbe.org/6eta PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6eta RCSB], [http://www.ebi.ac.uk/pdbsum/6eta PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6eta ProSAT]</span></td></tr>
+</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>
+<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=6eta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eta OCA], [http://pdbe.org/6eta PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6eta RCSB], [http://www.ebi.ac.uk/pdbsum/6eta PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6eta ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 10: / Line 11: @@
 == Function ==
 [[http://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 ==
+Protein crystal production is a major bottleneck in the structural characterization of proteins. To advance beyond large-scale screening, rational strategies for protein crystallization are crucial. Understanding how chemical anisotropy (or patchiness) of the protein surface, due to the variety of amino-acid side chains in contact with solvent, contributes to protein-protein contact formation in the crystal lattice is a major obstacle to predicting and optimizing crystallization. The relative scarcity of sophisticated theoretical models that include sufficient detail to link collective behavior, captured in protein phase diagrams, and molecular-level details, determined from high-resolution structural information, is a further barrier. Here, we present two crystal structures for the P23T + R36S mutant of gammaD-crystallin, each with opposite solubility behavior: one melts when heated, the other when cooled. When combined with the protein phase diagram and a tailored patchy particle model, we show that a single temperature-dependent interaction is sufficient to stabilize the inverted solubility crystal. This contact, at the P23T substitution site, relates to a genetic cataract and reveals at a molecular level the origin of the lowered and retrograde solubility of the protein. Our results show that the approach employed here may present a productive strategy for the rationalization of protein crystallization.
+Temperature-Dependent Interactions Explain Normal and Inverted Solubility in a gammaD-Crystallin Mutant.,Khan AR, James S, Quinn MK, Altan I, Charbonneau P, McManus JJ Biophys J. 2019 Sep 3;117(5):930-937. doi: 10.1016/j.bpj.2019.07.019. Epub 2019, Jul 19. PMID:31422822<ref>PMID:31422822</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6eta" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Crystallin 3D structures|Crystallin 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: James, S]]
 [[Category: Khan, A R]]

6eta

From Proteopedia

Current revision

Crystal Structure of Human Gamma-D crystallin Mutant P23T+R36S at Room Temperature

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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