alpha crystallins


Summary: A subclass of crystallins that provides the majority of refractive power and translucency to the lens (LENS, CRYSTALLINE) in VERTEBRATES. Alpha-crystallins also act as molecular chaperones that bind to denatured proteins, keep them in solution and thereby maintain the translucency of the lens. The proteins exist as large oligomers that are formed from ALPHA-CRYSTALLIN A CHAIN and ALPHA-CRYSTALLIN B CHAIN subunits.

Top Publications

  1. Liu J, Schlosser R, Ma W, Dong Z, Feng H, Liu L, et al. Human alphaA- and alphaB-crystallins prevent UVA-induced apoptosis through regulation of PKCalpha, RAF/MEK/ERK and AKT signaling pathways. Exp Eye Res. 2004;79:393-403 pubmed
    ..Together, our results for the first time reveal that by regulating multiple signaling pathways the two alpha-crystallins can prevent stress-induced apoptosis through different mechanisms. ..
  2. Ueda Y, Fukiage C, Shih M, Shearer T, David L. Mass measurements of C-terminally truncated alpha-crystallins from two-dimensional gels identify Lp82 as a major endopeptidase in rat lens. Mol Cell Proteomics. 2002;1:357-65 pubmed
    ..The methodology that allowed accurate mass measurements of proteins eluted from 2D gels should be useful to examine rapidly other post-translational modifications. ..
  3. Thampi P, Hassan A, Smith J, Abraham E. Enhanced C-terminal truncation of alphaA- and alphaB-crystallins in diabetic lenses. Invest Ophthalmol Vis Sci. 2002;43:3265-72 pubmed
    ..Loss of alphaA-crystallin chaperone activity seems to be related to truncation of the C-terminal amino acid residues. ..
  4. Horwitz J. Alpha-crystallin. Exp Eye Res. 2003;76:145-53 pubmed
    ..This review deals with some of the unique properties of the alpha-crystallins emphasizing especially what we don't know about its function and structure. ..
  5. Augusteyn R. alpha-crystallin: a review of its structure and function. Clin Exp Optom. 2004;87:356-66 pubmed
    ..It has been suggested that these functions are important for the maintenance of lens transparency and the prevention of cataract. ..
  6. Peterson J, Radke G, Takemoto L. Interaction of lens alpha and gamma crystallins during aging of the bovine lens. Exp Eye Res. 2005;81:680-9 pubmed
    ..conditions, gamma B crystallin from the aging bovine lens shows increased noncovalent associations with alpha crystallins, consistent with the possibility that such interactions play an important role in the transparent properties ..
  7. Pasta S, Raman B, Ramakrishna T, Rao C. Role of the C-terminal extensions of alpha-crystallins. Swapping the C-terminal extension of alpha-crystallin to alphaB-crystallin results in enhanced chaperone activity. J Biol Chem. 2002;277:45821-8 pubmed
    ..Our study demonstrates that the unstructured C-terminal extensions play a crucial role in the structure and chaperone activity, in addition to generally believed electrostatic "solubilizer" function. ..
  8. 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...
  9. Kumar M, Reddy P, Kumar P, Surolia I, Reddy G. Effect of dicarbonyl-induced browning on alpha-crystallin chaperone-like activity: physiological significance and caveats of in vitro aggregation assays. Biochem J. 2004;379:273-82 pubmed

More Information


  1. 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
  2. Rasmussen T, Kasimova M, Jiskoot W, van de Weert M. The chaperone-like protein alpha-crystallin dissociates insulin dimers and hexamers. Biochemistry. 2009;48:9313-20 pubmed publisher
    ..Furthermore, we propose that the dissociation of insulin is caused by the ability of alpha-crystallin to bind to the insulin self-association surfaces and thus stabilize insulin dimers and monomers. ..
  3. Biswas A, Das K. Alpha-crystallin assisted refolding of enzyme substrates: optimization of external parameters. Protein J. 2007;26:247-55 pubmed
    ..Refolding in presence of pre-incubated alpha-crystallin reveals that hydrophobicity had stronger influence on the refolding capacity of alpha-crystallin than its oligomeric size. ..
  4. Kiss A, Mirarefi A, Ramakrishnan S, Zukoski C, Devries A, Cheng C. Cold-stable eye lens crystallins of the Antarctic nototheniid toothfish Dissostichus mawsoni Norman. J Exp Biol. 2004;207:4633-49 pubmed
    ..Surprisingly, in cross-species chaperone assays, tuna alpha crystallins only partly protected toothfish gamma crystallins, while cow alpha crystallins completely failed to protect, ..
  5. Marini I, Moschini R, Del Corso A, Mura U. Chaperone-like features of bovine serum albumin: a comparison with alpha-crystallin. Cell Mol Life Sci. 2005;62:3092-9 pubmed
    ..Together, our results indicate that bovine serum albumin acts as a molecular chaperone and that, for its particular distribution, can be included in the extracellular chaperone family. ..
  6. Ponce A, Takemoto L. Screening of crystallin-crystallin interactions using microequilibrium dialysis. Mol Vis. 2005;11:752-7 pubmed
    ..These results show that microequilibrium dialysis can be used to demonstrate significant noncovalent interactions of alpha-crystallin and gamma-crystallin under true equilibrium conditions. ..
  7. 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. ..
  8. Reddy G, Kumar P, Kumar M. Chaperone-like activity and hydrophobicity of alpha-crystallin. IUBMB Life. 2006;58:632-41 pubmed
    ..We thus attempted to provide an overview on the role of hydrophobicity in chaperone-like activity of alpha-crystallin, the kind of evaluation done for the first time. ..
  9. 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. ..
  10. 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. ..
  11. Barral J, Broadley S, Schaffar G, Hartl F. Roles of molecular chaperones in protein misfolding diseases. Semin Cell Dev Biol. 2004;15:17-29 pubmed
    ..Increased chaperone expression can suppress the neurotoxicity of these molecules, suggesting possible therapeutic strategies. ..
  12. Yaung J, Kannan R, Wawrousek E, Spee C, Sreekumar P, Hinton D. Exacerbation of retinal degeneration in the absence of alpha crystallins in an in vivo model of chemically induced hypoxia. Exp Eye Res. 2008;86:355-65 pubmed publisher
    ..We conclude that lack of alpha-crystallins accentuates retinal degeneration in chemically induced hypoxia in vivo. ..
  13. Viteri G, Edwards A, de la Fuente J, Silva E. Study of the interaction between triplet riboflavin and the alpha-, betaH- and betaL-crystallins of the eye lens. Photochem Photobiol. 2003;77:535-40 pubmed
    ..The correlations found in this study confirm the importance of the Type-I photosensitizing mechanism of the crystallins, when RF acts as a sensitizer at low oxygen concentration, as can occur in the eye lens. ..
  14. Putilina T, Skouri Panet F, Prat K, Lubsen N, Tardieu A. Subunit exchange demonstrates a differential chaperone activity of calf alpha-crystallin toward beta LOW- and individual gamma-crystallins. J Biol Chem. 2003;278:13747-56 pubmed
    ..The changes in subunit exchange associated with the chaperone properties of alpha-crystallins toward the other lens crystallins demonstrate the dynamic character of the heat-activated alpha-crystallin structure. ..
  15. Takemoto L, Ponce A, Sorensen C. Age-dependent association of gamma-crystallins with aged alpha-crystallins from old bovine lens. Mol Vis. 2008;14:970-4 pubmed
    ..The results are consistent with the hypothesis that short-range, weak, attractive interactions between alpha- and gamma-crystallins are necessary for maximum transparency of the lens. ..
  16. Kashino S, Ovendale P, Izzo A, Campos Neto A. Unique model of dormant infection for tuberculosis vaccine development. Clin Vaccine Immunol. 2006;13:1014-21 pubmed
    ..tuberculosis strain 18b constitutes a simple and attractive animal model for evaluation of antituberculosis vaccines in the context of an M. tuberculosis-presensitized host, a prevailing condition among humans in need of a vaccine. ..
  17. Yamazaki Y, Fujii N, Sadakane Y, Fujii N. Differentiation and semiquantitative analysis of an isoaspartic acid in human alpha-Crystallin by postsource decay in a curved field reflectron. Anal Chem. 2010;82:6384-94 pubmed publisher
    ..Postsource decay experiments utilizing both the diagnostic ion and the characteristic fragment pattern could be applied to various kinds of peptides containing betaAsp. ..
  18. Masilamoni J, Jesudason E, Baben B, Jebaraj C, Dhandayuthapani S, Jayakumar R. Molecular chaperone alpha-crystallin prevents detrimental effects of neuroinflammation. Biochim Biophys Acta. 2006;1762:284-93 pubmed
    ..This study reiterates that alpha-crystallin therapy may serve as a potent pharmacological agent in neuroinflammation. ..
  19. Jagadeesan D, Mansoori U, Mandal P, Sundaresan A, Eswaramoorthy M. Hollow spheres to nanocups: tuning the morphology and magnetic properties of single-crystalline alpha-Fe2O3 nanostructures. Angew Chem Int Ed Engl. 2008;47:7685-8 pubmed publisher
  20. Shum W, Maleknia S, Downard K. Onset of oxidative damage in alpha-crystallin by radical probe mass spectrometry. Anal Biochem. 2005;344:247-56 pubmed
    ..The results are discussed in the context of available experimental and homology-modeled theoretical structures for the subunits of alpha-crystallin. ..
  21. Otani M, Ueki T, Kozuka S, Segawa M, Sano K, Inouye S. Characterization of a small heat shock protein, Mx Hsp16.6, of Myxococcus xanthus. J Bacteriol. 2005;187:5236-41 pubmed
    ..An insertion mutation in the hsp16.6 gene resulted in lower viability during heat shock and lower acquired thermotolerance. Therefore, it is likely that Mx Hsp16.6 plays critical roles in the heat shock response in M. xanthus. ..
  22. Devlin G, Carver J, Bottomley S. The selective inhibition of serpin aggregation by the molecular chaperone, alpha-crystallin, indicates a nucleation-dependent specificity. J Biol Chem. 2003;278:48644-50 pubmed
  23. Fu X, Li W, Mao Q, Chang Z. Disulfide bonds convert small heat shock protein Hsp16.3 from a chaperone to a non-chaperone: implications for the evolution of cysteine in molecular chaperones. Biochem Biophys Res Commun. 2003;308:627-35 pubmed
  24. de Miguel N, Echeverria P, Angel S. Differential subcellular localization of members of the Toxoplasma gondii small heat shock protein family. Eukaryot Cell. 2005;4:1990-7 pubmed
    ..These particular differences in the immunostaining patterns suggest that their targets and functions might be different. ..
  25. Rasmussen T, Tantipolphan R, van de Weert M, Jiskoot W. The molecular chaperone alpha-crystallin as an excipient in an insulin formulation. Pharm Res. 2010;27:1337-47 pubmed publisher
    ..alpha-Crystallin is proposed to bind specifically to pre-fibrillation species, thereby inhibiting fibrillation. This makes alpha-crystallin an interesting excipient for proteins with propensity to fibrillate. ..
  26. Chen J, Feige M, Franzmann T, Bepperling A, Buchner J. Regions outside the alpha-crystallin domain of the small heat shock protein Hsp26 are required for its dimerization. J Mol Biol. 2010;398:122-31 pubmed publisher
  27. Yan H, Harding J. Carnosine inhibits modifications and decreased molecular chaperone activity of lens alpha-crystallin induced by ribose and fructose 6-phosphate. Mol Vis. 2006;12:205-14 pubmed
  28. Tiffany J, Koretz J. Viscosity of alpha-crystallin solutions. Int J Biol Macromol. 2002;30:179-85 pubmed
    ..0 s(-1)) and high (94.5 s(-1)) shear rates, indicating low molecular interaction in solution. Arrhenius plots which might have indicated the size of the energy barrier to displacement of molecules or aggregates were inconclusive. ..
  29. Jagtap S, Rao M. Fluorescence study on interactions of alpha-crystallin with the molten globule state of 1, 4-beta-D-glucan glucanohydrolase from Thermomonospora sp. induced by guanidine hydrochloride. J Fluoresc. 2009;19:967-73 pubmed publisher
    ..Addition of alpha-crystallin to the molten globule-like intermediate of TSC (TSC-m complex) complex initiated the refolding of TSC with 69% recovery of the biological activity of the enzyme. ..
  30. Feasson L, Stockholm D, Freyssenet D, Richard I, Duguez S, Beckmann J, et al. Molecular adaptations of neuromuscular disease-associated proteins in response to eccentric exercise in human skeletal muscle. J Physiol. 2002;543:297-306 pubmed
    ..This remodelling response may limit the extent of muscle damage upon a subsequent mechanical stress. ..
  31. Zeiss C, Dubielzig R. Lentoid bodies in the avian retina. J Comp Pathol. 2006;135:243-8 pubmed
    ..The immunohistochemical data suggest that they arise from Müller cells. Association of lentoids with retinal damage supports the assertion that they arise following disruption of normal cell-cell communication. ..
  32. Sathish H, Koteiche H, McHaourab H. Binding of destabilized betaB2-crystallin mutants to alpha-crystallin: the role of a folding intermediate. J Biol Chem. 2004;279:16425-32 pubmed
    ..The ability of alpha-crystallin to detect subtle changes in the population of betaB2-crystallin excited states supports a central role for this chaperone in delaying aggregation and scattering in the lens. ..
  33. Yan H, Hui Y, Wang J. [The molecular chaperone function of alpha-crystallin in age-related cataract]. Yan Ke Xue Bao. 2005;21:156-60 pubmed
    ..A decrease in chaperone function from cataractous lenses has been showed in age-dependent and opacification-dependent fashion, which may play an important role in formation of cataract. ..
  34. Hook D, Harding J. The effect of modification of alpha-crystallin by prednisolone-21-hemisuccinate and fructose 6-phosphate on chaperone activity. Dev Ophthalmol. 2002;35:150-60 pubmed
    ..Tryptophan fluorescence provided evidence that the structure of alpha-crystallin had been modified by both compounds. ..
  35. Markossian K, Golub N, Chebotareva N, Asryants R, Naletova I, Muronetz V, et al. Comparative analysis of the effects of alpha-crystallin and GroEL on the kinetics of thermal aggregation of rabbit muscle glyceraldehyde-3-phosphate dehydrogenase. Protein J. 2010;29:11-25 pubmed publisher
  36. Benesch J, Ayoub M, Robinson C, Aquilina J. Small heat shock protein activity is regulated by variable oligomeric substructure. J Biol Chem. 2008;283:28513-7 pubmed publisher
    ..We propose that a bias toward monomeric substructure is responsible for the aberrant chaperone behavior associated with the alpha-crystallins in protein deposition diseases. ..
  37. Nores M, Prucca C, Quiroga R, Elias E, Cavallín L, Price A, et al. ORF-C4 from the early branching eukaryote Giardia lamblia displays characteristics of alpha-crystallin small heat-shock proteins. Biosci Rep. 2009;29:25-34 pubmed publisher
    ..In the present study, we show the potential role of ORF-C4 as a small chaperone which is involved in the response to stress (including encystation) in G. lamblia. ..
  38. Liu J, Schlosser R, Ma W, Dong Z, Feng H, Lui L, et al. Human alphaA- and alphaB-crystallins prevent UVA-induced apoptosis through regulation of PKCalpha, RAF/MEK/ERK and AKT signaling pathways. Exp Eye Res. 2004;79:393-403 pubmed
    ..Together, our results for the first time reveal that by regulating multiple signaling pathways the two alpha-crystallins can prevent stress-induced apoptosis through different mechanisms. ..
  39. Khidekel N, Arndt S, Lamarre Vincent N, Lippert A, Poulin Kerstien K, Ramakrishnan B, et al. A chemoenzymatic approach toward the rapid and sensitive detection of O-GlcNAc posttranslational modifications. J Am Chem Soc. 2003;125:16162-3 pubmed
    ..We anticipate that this general chemoenzymatic strategy will have broad application to the study of posttranslational modifications. ..
  40. Sharma D, Bose A, Shakila H, Das T, Tyagi J, Ramanathan V. Expression of mycobacterial cell division protein, FtsZ, and dormancy proteins, DevR and Acr, within lung granulomas throughout guinea pig infection. FEMS Immunol Med Microbiol. 2006;48:329-36 pubmed
    ..Both antigen staining and DNA detection from intact bacilli were useful for detecting intact mycobacteria in the absence of AFB. ..
  41. Truscott R. alpha crystallin: hot molecule, not just a lens packer. Clin Exp Optom. 2004;87:354-5 pubmed
  42. Skouri Panet F, Quevillon Cheruel S, Michiel M, Tardieu A, Finet S. sHSPs under temperature and pressure: the opposite behaviour of lens alpha-crystallins and yeast HSP26. Biochim Biophys Acta. 2006;1764:372-83 pubmed
  43. Horwitz J, Huang Q, Ding L. The native oligomeric organization of alpha-crystallin, is it necessary for its chaperone function?. Exp Eye Res. 2004;79:817-21 pubmed
    ..The data suggest that the native oligomeric state of alpha-crystallin may not be essential for its ability to suppress non-specific aggregation...
  44. Yaung J, Jin M, Barron E, Spee C, Wawrousek E, Kannan R, et al. alpha-Crystallin distribution in retinal pigment epithelium and effect of gene knockouts on sensitivity to oxidative stress. Mol Vis. 2007;13:566-77 pubmed
    ..Lack of alpha-crystallins renders RPE cells more susceptible to apoptosis from oxidative stress. Mitochondrial alpha-crystallins may play an important role in the protection from increased susceptibility of RPE in oxidative stress. ..
  45. Puttaiah S, Biswas A, Staniszewska M, Nagaraj R. Methylglyoxal inhibits glycation-mediated loss in chaperone function and synthesis of pentosidine in alpha-crystallin. Exp Eye Res. 2007;84:914-21 pubmed
    ..Together, these data suggest that in the aging lens, MGO inhibits glycation-mediated pentosidine synthesis and the loss of chaperone function of alpha-crystallin. ..
  46. Yang Y, Zeng J, Gao C, Krull U. Stabilization and re-activation of trapped enzyme by immobilized heat shock protein and molecular chaperones. Biosens Bioelectron. 2003;18:311-7 pubmed
    ..The results suggest that immobilized molecular chaperones such as HSP 70 may provide some potential for stabilization and re-activation of enzymes that are trapped in thin aqueous films for applications in biosensors and reactors. ..
  47. Surolia I, Sinha S, Sarkar D, Reddy P, Reddy G, Surolia A. Concurrence of Danish dementia and cataract: insights from the interactions of dementia associated peptides with eye lens alpha-crystallin. PLoS ONE. 2008;3:e2927 pubmed publisher
  48. Avilov S, Aleksandrov N, Demchenko A. Quaternary structure of alpha-crystallin is necessary for the binding of unfolded proteins: a surface plasmon resonance study. Protein Pept Lett. 2004;11:41-8 pubmed
    ..We observe that these subunits, in contrast to alpha-crystallin oligomers, do not bind unfolded protein. Our data indicate that quaternary structure of alpha-crystallin is necessary for its chaperone-like activity. ..
  49. Huey K, Meador B. Contribution of IL-6 to the Hsp72, Hsp25, and alphaB-crystallin [corrected] responses to inflammation and exercise training in mouse skeletal and cardiac muscle. J Appl Physiol (1985). 2008;105:1830-6 pubmed publisher
  50. Latham J, Stein R, Bornhop D, McHaourab H. Free-solution label-free detection of alpha-crystallin chaperone interactions by back-scattering interferometry. Anal Chem. 2009;81:1865-71 pubmed publisher
    ..This work demonstrates that BSI can be extended to screen libraries of disease-related mutants to quantify changes in affinity and/or kinetics of binding. ..
  51. Regini J, Grossmann J, Burgio M, Malik N, Koretz J, Hodson S, et al. Structural changes in alpha-crystallin and whole eye lens during heating, observed by low-angle X-ray diffraction. J Mol Biol. 2004;336:1185-94 pubmed
    ..Upon cooling, this effect was found to be irreversible over 11 hours. Qualitatively similar results were observed for alpha-crystallin solutions at a variety of lower concentrations. ..
  52. Peterson J, Young M, Takemoto L. Probing alpha-crystallin structure using chemical cross-linkers and mass spectrometry. Mol Vis. 2004;10:857-66 pubmed
  53. Yan H, Yao L, Hui Y. [Decreased chaperone activity of alpha-crystallin by carbamylation in vitro]. Yan Ke Xue Bao. 2004;20:264-7 pubmed
    ..The alpha-crystallin can be modified in vitro by carbamylation through a high-molecular-weight aggregates formation. The loss of its chaperone activity may result from carbamylation-induced aggregation. ..