gamma crystallins


Summary: A subclass of crystallins that found in the lens (LENS, CRYSTALLINE) of VERTEBRATES. Gamma-crystallins are similar in structure to BETA-CRYSTALLINS in that they both form into a Greek key-like structure. They are composed of monomeric subunits.

Top Publications

  1. Bu L, Yan S, Jin M, Jin Y, Yu C, Xiao S, et al. The gamma S-crystallin gene is mutated in autosomal recessive cataract in mouse. Genomics. 2002;80:38-44 pubmed
    ..This finding suggests that CRYGS is not only a lens structural protein, but is also likely to be involved in epithelial cell proliferation, apoptosis, and migration. ..
  2. Fan J, Fariss R, Purkiss A, Slingsby C, Sandilands A, Quinlan R, et al. Specific interaction between lens MIP/Aquaporin-0 and two members of the gamma-crystallin family. Mol Vis. 2005;11:76-87 pubmed
    ..This raises the possibility of MIP playing a structural role in the organization of gamma-crystallins in rodent lens fibers and/or that gammaE- and gammaF-crystallin may have a specific role in MIP function in the rodent lens. ..
  3. Giancola C, Pizzo E, Di Maro A, Cubellis M, D Alessio G. Preparation and characterization of geodin. A betagamma-crystallin-type protein from a sponge. FEBS J. 2005;272:1023-35 pubmed
    ..These results suggest that the crystallin-type structural scaffold, employed in the evolution of bacteria and moulds, was successfully recruited very early in the evolution of metazoa. ..
  4. Yang Y, Chauhan B, Cveklova K, Cvekl A. Transcriptional regulation of mouse alphaB- and gammaF-crystallin genes in lens: opposite promoter-specific interactions between Pax6 and large Maf transcription factors. J Mol Biol. 2004;344:351-68 pubmed
  5. Meehan S, Berry Y, Luisi B, Dobson C, Carver J, MacPhee C. Amyloid fibril formation by lens crystallin proteins and its implications for cataract formation. J Biol Chem. 2004;279:3413-9 pubmed
    ..The ability of the crystallins to convert into fibrils under destabilizing conditions suggests that this process could contribute to the development of cataract with aging. ..
  6. Zarina S, Abbasi A, Zaidi Z. Primary structure of beta s-crystallin from human lens. Biochem J. 1992;287 ( Pt 2):375-81 pubmed
    ..The structure, evolutionary characteristics and role of beta s-crystallin in lens are discussed. ..
  7. Xu W, Zheng S, Dong Q, Cai S, Yao K, Zhang S. [Ultrastructure and crystallin mutant molecular modeling of hereditary coralliform cataract]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2005;34:243-7 pubmed
    ..It is possible that the gammaD-crystallin P23T mutant is associated with abnormal crystals in lens and disorganization of lens epithelial cells. ..
  8. Wang X, Garcia C, Shui Y, Beebe D. Expression and regulation of alpha-, beta-, and gamma-crystallins in mammalian lens epithelial cells. Invest Ophthalmol Vis Sci. 2004;45:3608-19 pubmed
    ..After stress, most alphaA- and alphaB-crystallin subunits are not in the same macromolecular complexes. ..
  9. Shentu X, Yao K, Sun Z, Xu W. [Study on ultrastructure changes and the genetic locus for a special phenotype cataract]. Zhonghua Yan Ke Za Zhi. 2004;40:306-10 pubmed
    ..There were characteristic alterations to the lens fiber cells of this special phenotype ADCC and the CRYGD gene might be the disease-associated. ..

More Information


  1. Hansen L, Yao W, Eiberg H, Kjaer K, Baggesen K, Hejtmancik J, et al. Genetic heterogeneity in microcornea-cataract: five novel mutations in CRYAA, CRYGD, and GJA8. Invest Ophthalmol Vis Sci. 2007;48:3937-44 pubmed
  2. Chen J, Toptygin D, Brand L, King J. Mechanism of the efficient tryptophan fluorescence quenching in human gammaD-crystallin studied by time-resolved fluorescence. Biochemistry. 2008;47:10705-21 pubmed publisher
  3. Wu Z, Delaglio F, Wyatt K, Wistow G, Bax A. Solution structure of (gamma)S-crystallin by molecular fragment replacement NMR. Protein Sci. 2005;14:3101-14 pubmed
    ..The method used for solving the gammaS structure relies on the recently introduced molecular fragment replacement method, which capitalizes on the large database of protein structures previously solved by X-ray crystallography and NMR. ..
  4. Robertson L, David L, Riviere M, Wilmarth P, Muir M, Morton J. Susceptibility of ovine lens crystallins to proteolytic cleavage during formation of hereditary cataract. Invest Ophthalmol Vis Sci. 2008;49:1016-22 pubmed publisher
    ..The ovine hereditary cataract is a useful nonrodent model to study the role of calpain proteolysis in cataract formation...
  5. Pande A, Annunziata O, Asherie N, Ogun O, Benedek G, Pande J. Decrease in protein solubility and cataract formation caused by the Pro23 to Thr mutation in human gamma D-crystallin. Biochemistry. 2005;44:2491-500 pubmed
    ..These findings may help develop a strategy for the rational design of small molecule inhibitors of this type of condensed phase. ..
  6. Khan A, Aldahmesh M, Ghadhfan F, Al Mesfer S, Alkuraya F. Founder heterozygous P23T CRYGD mutation associated with cerulean (and coralliform) cataract in 2 Saudi families. Mol Vis. 2009;15:1407-11 pubmed
    ..Coralliform cataract can represent variable expressivity for the same mutation rather than a distinct entity. ..
  7. Basak A, Bateman O, Slingsby C, Pande A, Asherie N, Ogun O, et al. High-resolution X-ray crystal structures of human gammaD crystallin (1.25 A) and the R58H mutant (1.15 A) associated with aculeiform cataract. J Mol Biol. 2003;328:1137-47 pubmed
    ..The results presented here are also important as they are the first high-resolution X-ray structures of human gamma crystallins.
  8. Sun H, Ma Z, Li Y, Liu B, Li Z, Ding X, et al. Gamma-S crystallin gene (CRYGS) mutation causes dominant progressive cortical cataract in humans. J Med Genet. 2005;42:706-10 pubmed
    ..This report is the first description of a mutation in CRYGS with autosomal dominant cataract in humans. ..
  9. Flaugh S, Kosinski Collins M, King J. Interdomain side-chain interactions in human gammaD crystallin influencing folding and stability. Protein Sci. 2005;14:2030-43 pubmed
    ..Such damage may generate partially unfolded, aggregation- prone conformations of HgammaD-Crys that could be significant in cataract. ..
  10. Salim A, Bano A, Zaidi Z. Prediction of possible sites for posttranslational modifications in human gamma crystallins: effect of glycation on the structure of human gamma-B-crystallin as analyzed by molecular modeling. Proteins. 2003;53:162-73 pubmed
  11. Li F, Wang S, Gao C, Liu S, Zhao B, Zhang M, et al. Mutation G61C in the CRYGD gene causing autosomal dominant congenital coralliform cataracts. Mol Vis. 2008;14:378-86 pubmed
    ..This is the first reported case of a congenital coralliform cataract phenotype associated with the mutation of Gly61Cys (P.G61C) in the CRYGD gene; it demonstrates a possible mechanism of action for the mutant gene. ..
  12. Goishi K, Shimizu A, Najarro G, Watanabe S, Rogers R, Zon L, et al. AlphaA-crystallin expression prevents gamma-crystallin insolubility and cataract formation in the zebrafish cloche mutant lens. Development. 2006;133:2585-93 pubmed
    ..In addition, these results show that proteomics is a valuable tool for detecting protein alterations in zebrafish. ..
  13. Chen J, Flaugh S, Callis P, King J. Mechanism of the highly efficient quenching of tryptophan fluorescence in human gammaD-crystallin. Biochemistry. 2006;45:11552-63 pubmed
  14. Liang J. Interactions and chaperone function of alphaA-crystallin with T5P gammaC-crystallin mutant. Protein Sci. 2004;13:2476-82 pubmed
  15. McManus J, Lomakin A, Ogun O, Pande A, Basan M, Pande J, et al. Altered phase diagram due to a single point mutation in human gammaD-crystallin. Proc Natl Acad Sci U S A. 2007;104:16856-61 pubmed
  16. Papanikolopoulou K, Mills Henry I, Thol S, Wang Y, Gross A, Kirschner D, et al. Formation of amyloid fibrils in vitro by human gammaD-crystallin and its isolated domains. Mol Vis. 2008;14:81-9 pubmed
    ..Investigations of early stages in cataract formation within the lens will be required to assess whether amyloid fibrils play a role in the initiation of cataract in vivo. ..
  17. Thurston G. Liquid-liquid phase separation and static light scattering of concentrated ternary mixtures of bovine alpha and gammaB crystallins. J Chem Phys. 2006;124:134909 pubmed
    ..By applying this analysis to the experimental tie lines we estimate the magnitude of the saddlelike component of the free energy near the aqueous-gammaB critical point. ..
  18. Gu F, Li R, Ma X, Shi L, Huang S, Ma X. A missense mutation in the gammaD-crystallin gene CRYGD associated with autosomal dominant congenital cataract in a Chinese family. Mol Vis. 2006;12:26-31 pubmed
    ..Bioinformatic analyses also showed that a highly conserved region was located at Arg14. This study is the first reported case with phenotype of coralliform/nuclear cataract that associated with the mutation of Arg14Cys (R14C) CRYGD. ..
  19. Evans P, Wyatt K, Wistow G, Bateman O, Wallace B, Slingsby C. The P23T cataract mutation causes loss of solubility of folded gammaD-crystallin. J Mol Biol. 2004;343:435-44 pubmed
    ..These results suggest that insolubility, rather than loss of stability, is the primary basis for P23T congenital cataracts. ..
  20. Purkiss A, Bateman O, Wyatt K, Wilmarth P, David L, Wistow G, et al. Biophysical properties of gammaC-crystallin in human and mouse eye lens: the role of molecular dipoles. J Mol Biol. 2007;372:205-22 pubmed
    ..It is suggested that changes in surface residues have allowed adaptation for the differing needs of human and mouse lenses. ..
  21. Kosinski Collins M, Flaugh S, King J. Probing folding and fluorescence quenching in human gammaD crystallin Greek key domains using triple tryptophan mutant proteins. Protein Sci. 2004;13:2223-35 pubmed
    ..This species is a candidate for the partially folded intermediate in the in vitro aggregation pathway of HgammaD-Crys. ..
  22. Weadick C, Chang B. Molecular evolution of the betagamma lens crystallin superfamily: evidence for a retained ancestral function in gamma N crystallins?. Mol Biol Evol. 2009;26:1127-42 pubmed publisher
    ..our analysis as outgroups, we confirmed the phylogenetic position of the gamma N family as sister to other gamma crystallins. Using maximum likelihood codon models to estimate lineage-specific nonsynonymous-to-synonymous rate ratios ..
  23. Plotnikova O, Kondrashov F, Vlasov P, Grigorenko A, Ginter E, Rogaev E. 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;81:32-43 pubmed publisher
  24. Stradner A, Foffi G, Dorsaz N, Thurston G, Schurtenberger P. New insight into cataract formation: enhanced stability through mutual attraction. Phys Rev Lett. 2007;99:198103 pubmed
  25. Yao K, Jin C, Zhu N, Wang W, Wu R, Jiang J, et al. A nonsense mutation in CRYGC associated with autosomal dominant congenital nuclear cataract in a Chinese family. Mol Vis. 2008;14:1272-6 pubmed
  26. Zhang L, Gong B, Tong J, Fan D, Chiang S, Lou D, et al. A novel gammaD-crystallin mutation causes mild changes in protein properties but leads to congenital coralliform cataract. Mol Vis. 2009;15:1521-9 pubmed
    ..R15S possessed similar properties to the wild type gammaD-crystallin, but its predicted increase of hydrophobicity and putative phosphorylation site could lead to protein aggregation, subsequently causing opacification in lens. ..
  27. Shimeld S, Purkiss A, Dirks R, Bateman O, Slingsby C, Lubsen N. Urochordate betagamma-crystallin and the evolutionary origin of the vertebrate eye lens. Curr Biol. 2005;15:1684-9 pubmed
  28. Takemoto L, Ponce A. Decreased association of aged alpha crystallins with gamma crystallins. Exp Eye Res. 2006;83:793-7 pubmed
    Previous studies have demonstrated non-covalent interactions of alpha crystallins with gamma crystallins, under true equilibrium conditions...
  29. Mackay D, Andley U, Shiels A. A missense mutation in the gammaD crystallin gene (CRYGD) associated with autosomal dominant "coral-like" cataract linked to chromosome 2q. Mol Vis. 2004;10:155-62 pubmed
    ..This study has identified an eighth type of cataract morphology associated with CRYGD and suggests that a CRYGD mutation may underlie the historically important "coralliform" cataract first reported in 1895. ..
  30. Biswas A, Das K. Role of ATP on the interaction of alpha-crystallin with its substrates and its implications for the molecular chaperone function. J Biol Chem. 2004;279:42648-57 pubmed
    ..The implication of the ATP-induced reversible protein-protein association at physiological temperatures on the functional role of alpha-crystallin in vivo is discussed. ..
  31. Fu L, Liang J. Alteration of protein-protein interactions of congenital cataract crystallin mutants. Invest Ophthalmol Vis Sci. 2003;44:1155-9 pubmed
    ..The results clearly indicate that crystallin mutations involved in congenital cataracts altered protein-protein interactions, which may contribute to decreased protein solubility and formation of cataract. ..
  32. Chauhan B, Yang Y, Cveklova K, Cvekl A. Functional interactions between alternatively spliced forms of Pax6 in crystallin gene regulation and in haploinsufficiency. Nucleic Acids Res. 2004;32:1696-709 pubmed
    ..g. mafa/c-maf. ..
  33. Pande A, Zhang J, Banerjee P, Puttamadappa S, Shekhtman A, Pande J. NMR study of the cataract-linked P23T mutant of human gammaD-crystallin shows minor changes in hydrophobic patches that reflect its retrograde solubility. Biochem Biophys Res Commun. 2009;382:196-9 pubmed publisher
    ..The data provide a structural basis for explaining the retrograde solubility of P23T by (a) identifying possible "sticky" patches on the surface of P23T and (b) highlighting their asymmetric distribution. ..
  34. Talla V, Narayanan C, Srinivasan N, Balasubramanian D. Mutation causing self-aggregation in human gammaC-crystallin leading to congenital cataract. Invest Ophthalmol Vis Sci. 2006;47:5212-7 pubmed
    ..These results support the idea that unfolding or structural destabilization is not always necessary for crystallin-associated cataractogenesis. ..
  35. Zenteno J, Morales M, Moran Barroso V, Sanchez Navarro A. CRYGD gene analysis in a family with autosomal dominant congenital cataract: evidence for molecular homogeneity and intrafamilial clinical heterogeneity in aculeiform cataract. Mol Vis. 2005;11:438-42 pubmed
    ..To our knowledge, this is the first example of phenotypic heterogeneity associated with the Arg 58 His CRYGD mutation. ..
  36. Muller C, Wohlke A, Distl O. Evaluation of canine gamma-crystallin C (CRYGC) with hereditary cataracts in Entlebucher mountain dogs. Anim Genet. 2006;37:422-3 pubmed
  37. Gu J, Qi Y, Wang L, Wang J, Shi L, Lin H, et al. A new congenital nuclear cataract caused by a missense mutation in the gammaD-crystallin gene (CRYGD) in a Chinese family. Mol Vis. 2005;11:971-6 pubmed
    ..This finding is an additional indication that there may be phenotypic heterogeneity of cataract, especially in different races. ..
  38. Gu J, Qi Y, Lin H, Li X, Wang J, Meng W, et al. [Autosomal dominant congenital golden crystal nuclear cataract caused by a missense mutation in gammaD crystallin gene (CRYGD) in a Chinese family]. Zhonghua Yan Ke Za Zhi. 2006;42:913-7 pubmed
    ..This finding indicates that the presence of phenotypic heterogeneity of cataract, especially in different races. This is the first report of congenital cataract caused by R36S mutation in CRYGD gene. ..
  39. Sandilands A, Hutcheson A, Long H, Prescott A, Vrensen G, Löster J, et al. Altered aggregation properties of mutant gamma-crystallins cause inherited cataract. EMBO J. 2002;21:6005-14 pubmed
    ..The mutant gamma-crystallins initially disrupt nuclear function, but then this progresses to a full cataract phenotype. ..
  40. Rajaram N, Kerppola T. Synergistic transcription activation by Maf and Sox and their subnuclear localization are disrupted by a mutation in Maf that causes cataract. Mol Cell Biol. 2004;24:5694-709 pubmed
    ..The mislocalization of normal cellular proteins to these foci provides a potential explanation for the dominant disease phenotype of the R288P mutation in Maf. ..
  41. Santana A, Waiswol M, Arcieri E, Cabral de Vasconcellos J, Barbosa de Melo M. Mutation analysis of CRYAA, CRYGC, and CRYGD associated with autosomal dominant congenital cataract in Brazilian families. Mol Vis. 2009;15:793-800 pubmed
    ..A new polymorphism (S119S) in CRYGC was also observed in one family. The analysis of nine families excluded possible mutations in the crystallin genes, suggesting that other genes could be involved with congenital cataract. ..
  42. Zhang L, Yam G, Fan D, Tam P, Lam D, Pang C. A novel deletion variant of gammaD-crystallin responsible for congenital nuclear cataract. Mol Vis. 2007;13:2096-104 pubmed
  43. Messina Baas O, Gonzalez Huerta L, Cuevas Covarrubias S. Two affected siblings with nuclear cataract associated with a novel missense mutation in the CRYGD gene. Mol Vis. 2006;12:995-1000 pubmed
    ..In this study we describe the mutation c.320A > C (E107A) in the CRYGD gene associated with nuclear congenital cataract. Haplotype analysis strongly suggests that the origin of the mutation was transmitted through the mother. ..
  44. Di Maro A, Pizzo E, Cubellis M, D Alessio G. An intron-less betagamma-crystallin-type gene from the sponge Geodia cydonium. Gene. 2002;299:79-82 pubmed
    ..These findings are discussed in the light of the debate between the introns-late and introns-early theories. ..
  45. Jung J, Byeon I, Wang Y, King J, Gronenborn A. The structure of the cataract-causing P23T mutant of human gammaD-crystallin exhibits distinctive local conformational and dynamic changes. Biochemistry. 2009;48:2597-609 pubmed publisher
    ..The data support structural changes that may initiate aggregation or polymerization by the mutant protein. ..
  46. Klopp N, Loster J, Graw J. Characterization of a 1-bp deletion in the gammaE-crystallin gene leading to a nuclear and zonular cataract in the mouse. Invest Ophthalmol Vis Sci. 2001;42:183-7 pubmed
    ..Because several members of this group have been confirmed as mutations in the gene cluster coding for gamma-crystallins (CRYG:), these genes were now tested as candidates for Cat2(nz)...
  47. Lapko V, Smith D, Smith J. S-methylated cysteines in human lens gamma S-crystallins. Biochemistry. 2002;41:14645-51 pubmed
    ..Evidence of more S-methylation in soluble than in insoluble gammaS-crystallins supports the contention that S-methylation of gammaS-crystallin inhibits protein insolubilization and may offer protection against cataract. ..
  48. Nandrot E, Slingsby C, Basak A, Cherif Chefchaouni M, Benazzouz B, Hajaji Y, et al. Gamma-D crystallin gene (CRYGD) mutation causes autosomal dominant congenital cerulean cataracts. J Med Genet. 2003;40:262-7 pubmed
    ..Furthermore, this is the first report of a mutation in this gene resulting in autosomal dominant congenital cerulean cataracts. ..
  49. Graw J, Neuhäuser Klaus A, Klopp N, Selby P, Löster J, Favor J. Genetic and allelic heterogeneity of Cryg mutations in eight distinct forms of dominant cataract in the mouse. Invest Ophthalmol Vis Sci. 2004;45:1202-13 pubmed
    ..The unequal distribution of mutations suggests hot spots in the Cryg genes. The overall high number of mutations in these genes demonstrates their central role in the maintenance of lens transparency. ..
  50. Li L, Chang B, Cheng C, Chang D, Hawes N, Xia C, et al. Dense nuclear cataract caused by the gammaB-crystallin S11R point mutation. Invest Ophthalmol Vis Sci. 2008;49:304-9 pubmed publisher
    ..Subsequent activation of calcium-dependent protein degradation and degeneration of inner mature fiber cells led to the dense nuclear cataract. ..
  51. Shentu X, Yao K, Xu W, Zheng S, Hu S, Gong X. Special fasciculiform cataract caused by a mutation in the gammaD-crystallin gene. Mol Vis. 2004;10:233-9 pubmed
    ..It appeared to be caused by a missense mutation in the CRYGD gene, further supporting the notion that alterations to CRYG play an important factor in human cataract formation. ..
  52. Flaugh S, Kosinski Collins M, King J. Contributions of hydrophobic domain interface interactions to the folding and stability of human gammaD-crystallin. Protein Sci. 2005;14:569-81 pubmed
    ..Specificity of domain interface interactions is likely important for preventing incorrect associations in the high protein concentrations of the lens nucleus. ..
  53. Flaugh S, Mills I, King J. Glutamine deamidation destabilizes human gammaD-crystallin and lowers the kinetic barrier to unfolding. J Biol Chem. 2006;281:30782-93 pubmed
    ..Such effects may be significant for cataract formation by inducing protein aggregation or insolubility. ..