Skip to main content
SpringerLink
Log in

α-Crystallins are small heat shock proteins: Functional and structural properties

  • Review
  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

During its life cycle, a cell can be subjected to various external negative effects. Many proteins provide cell protection, including small heat shock proteins (sHsp) that have chaperone-like activity. These proteins have several important functions involving prevention of apoptosis and retention of cytoskeletal integrity; also, sHsp take part in the recovery of enzyme activity. The action mechanism of sHsp is based on the binding of hydrophobic regions exposed to the surface of a molten globule. α-Crystallins presented in chordate cells as two αAand αB-isoforms are the most studied small heat shock proteins. In this review, we describe the main functions of α-crystallins, features of their secondary and tertiary structures, and examples of their partners in protein–protein interactions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

ACD:

α-crystallin domain

cryo-EM:

cryoelectron microscopy

CTD:

C-terminal domain

EM:

electron microscopy

NTD:

N-terminal domain

RNP:

ribonucleoprotein

SMN:

survival of motor neuron

TEM:

transmission electron microscopy

TOM20:

translocase of the outer membrane

VDAC:

voltage-dependent anion channel

References

  1. Maaroufi, H., and Tanguay, R. M. (2013) Analysis and phylogeny of small heat shock proteins from marine viruses and their cyanobacteria host, PLoS One, 8, e81207.

    Article  CAS  Google Scholar 

  2. Buchner, J., Grallert, H., and Jakob, U. (1998) Analysis of chaperone function using citrate synthase as non-native substrate protein, Methods Enzymol., 290, 323–338.

    Article  CAS  PubMed  Google Scholar 

  3. Ingolia, T. D., and Craig, E. A. (1982) Four small Drosophila heat shock proteins are related to each other and to mammalian alpha-crystallin, Proc. Natl. Acad. Sci. USA, 79, 2360–2364.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Mani, N., Bhandari, S., Moreno, R., Hu, L., Prasad, B. V., and Suguna, K. (2016) Multiple oligomeric structures of a bacterial small heat shock protein, Sci. Rep., 6, 24019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Eaton, P., Fuller, W., Bell, J. R., and Shattock, M. J. (2001) AlphaB crystallin translocation and phosphorylation: signal transduction pathways and preconditioning in the isolated rat heart, J. Mol. Cell. Cardiol., 33, 1659–1671.

    Article  CAS  PubMed  Google Scholar 

  6. Krishnamoorthy, V., Donofrio, A. J., and Martin, J. L. (2013) O-GlcNAcylation of aB-crystallin regulates its stress-induced translocation and cytoprotection, Mol. Cell. Biochem., 379, 59–68.

    Article  CAS  PubMed  Google Scholar 

  7. Armstrong, S. C., Shivell, C. L., and Ganote, C. E. (2000) Differential translocation or phosphorylation of alpha B crystallin cannot be detected in ischemically preconditioned rabbit cardiomyocytes, J. Mol. Cell. Cardiol., 32, 1301–1314.

    Article  CAS  PubMed  Google Scholar 

  8. Clarke, J. P., and Mearow, K. M. (2013) Cell stress promotes the association of phosphorylated HspB1 with Factin, PLoS One, 8, e68978.

    Article  CAS  Google Scholar 

  9. Lindner, R. A., Carver, J. A., Ehrnsperger, M., Buchner, J., Esposito, G., Behlke, J., Lutsch, G., Kotlyarov, A., and Gaestel, M. (2000) Mouse Hsp25, a small shock protein. The role of its C-terminal extension in oligomerization and chaperone action, Eur. J. Biochem. FEBS, 267, 1923–1932.

    CAS  Google Scholar 

  10. Van Montfort, R. L., Basha, E., Friedrich, K. L., Slingsby, C., and Vierling, E. (2001) Crystal structure and assembly of a eukaryotic small heat shock protein, Nat. Struct. Biol., 8, 1025–1030.

    Article  PubMed  CAS  Google Scholar 

  11. Skouri-Panet, F., Michiel, M., Ferard, C., Duprat, E., and Finet, S. (2012) Structural and functional specificity of small heat shock protein HspB1 and HspB4, two cellular partners of HspB5: role of the in vitro hetero-complex formation in chaperone activity, Biochimie, 94, 975–984.

    CAS  PubMed  Google Scholar 

  12. Pasta, S. Y., Raman, B., Ramakrishna, T., and Rao, C. M. (2004) The IXI/V motif in the C-terminal extension of alpha-crystallins: alternative interactions and oligomeric assemblies, Mol. Vis., 10, 655–662.

    CAS  PubMed  Google Scholar 

  13. Poulain, P., Gelly, J.-C., and Flatters, D. (2010) Detection and architecture of small heat shock protein monomers, PLoS One, 5, e9990.

    Article  CAS  Google Scholar 

  14. Lambert, H., Charette, S. J., Bernier, A. F., Guimond, A., and Landry, J. (1999) HSP27 multimerization mediated by phosphorylation-sensitive intermolecular interactions at the amino terminus, J. Biol. Chem., 274, 9378–9385.

    Article  CAS  PubMed  Google Scholar 

  15. Sudnitsyna, M. V., Mymrikov, E. V., Seit-Nebi, A. S., and Gusev, N. B. (2012) The role of intrinsically disordered regions in the structure and functioning of small heat shock proteins, Curr. Protein Pept. Sci., 13, 76–85.

    Article  CAS  PubMed  Google Scholar 

  16. Lelj-Garolla, B., and Mauk, A. G. (2012) Roles of the Nand C-terminal sequences in Hsp27 self-association and chaperone activity, Protein Sci. Publ. Protein Soc., 21, 122133.

    Article  CAS  Google Scholar 

  17. Ito, H., Okamoto, K., Nakayama, H., Isobe, T., and Kato, K. (1997) Phosphorylation of aB-crystallin in response to various types of stress, J. Biol. Chem., 272, 29934–29941.

    Article  CAS  PubMed  Google Scholar 

  18. Vertii, A., Hakim, C., Kotlyarov, A., and Gaestel, M. (2006) Analysis of properties of small heat shock protein Hsp25 in MAPK-activated protein kinase 2 (MK2)-deficient cells: MK2-dependent insolubilization of Hsp25 oligomers correlates with susceptibility to stress, J. Biol. Chem., 281, 26966–26975.

    Article  CAS  PubMed  Google Scholar 

  19. Landry, J., Lambert, H., Zhou, M., Lavoie, J. N., Hickey, E., Weber, L. A., and Anderson, C. W. (1992) Human HSP27 is phosphorylated at serines 78 and 82 by heat shock and mitogen-activated kinases that recognize the same amino acid motif as S6 kinase II, J. Biol. Chem., 267, 794803.

    Google Scholar 

  20. Ecroyd, H., Meehan, S., Horwitz, J., Aquilina, J. A., Benesch, J. L. P., Robinson, C. V., Macphee, C. E., and Carver, J. A. (2007) Mimicking phosphorylation of aBcrystallin affects its chaperone activity, Biochem. J., 401, 129–141.

    Article  CAS  PubMed  Google Scholar 

  21. Rogalla, T., Ehrnsperger, M., Preville, X., Kotlyarov, A., Lutsch, G., Ducasse, C., Paul, C., Wieske, M., Arrigo, A. P., Buchner, J., and Gaestel, M. (1999) Regulation of Hsp27 oligomerization, chaperone function, and protective activity against oxidative stress/tumor necrosis factor alpha by phosphorylation, J. Biol. Chem., 274, 18947–18956.

    CAS  PubMed  Google Scholar 

  22. Ito, H., Kamei, K., Iwamoto, I., Inaguma, Y., Nohara, D., and Kato, K. (2001) Phosphorylation-induced change of the oligomerization state of aB-crystallin, J. Biol. Chem., 276, 5346–5352.

    Article  CAS  PubMed  Google Scholar 

  23. Mymrikov, E. V., Seit-Nebi, A. S., and Gusev, N. B. (2011) Heterooligomeric complexes of human small heat shock proteins, Cell Stress Chaperones, 17, 157–169.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Delbecq, S. P., Rosenbaum, J. C., and Klevit, R. E. (2015) A mechanism of subunit recruitment in human small heat shock protein oligomers, Biochemistry, 54, 4276–4284.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Aquilina, J. A., Shrestha, S., Morris, A. M., and Ecroyd, H. (2013) Structural and functional aspects of heterooligomers formed by the small heat shock proteins aBcrystallin and HSP27, J. Biol. Chem., 288, 13602–13609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kamradt, M. C., Lu, M., Werner, M. E., Kwan, T., Chen, F., Strohecker, A., Oshita, S., Wilkinson, J. C., Yu, C., Oliver, P. G., Duckett, C. S., Buchsbaum, D. J., LoBuglio, A. F., Jordan, V. C., and Cryns, V. L. (2005) The small heat shock protein alpha B-crystallin is a novel inhibitor of TRAIL-induced apoptosis that suppresses the activation of caspase-3, J. Biol. Chem., 280, 11059–11066.

    Article  CAS  PubMed  Google Scholar 

  27. Mehlen, P., Schulze-Osthoff, K., and Arrigo, A. P. (1996) Small stress proteins as novel regulators of apoptosis. Heat shock protein 27 blocks Fas/APO-1and staurosporineinduced cell death, J. Biol. Chem., 271, 16510–16514.

    Article  CAS  PubMed  Google Scholar 

  28. Bruey, J. M., Ducasse, C., Bonniaud, P., Ravagnan, L., Susin, S. A., Diaz-Latoud, C., Gurbuxani, S., Arrigo, A. P., Kroemer, G., Solary, E., and Garrido, C. (2000) Hsp27 negatively regulates cell death by interacting with cytochrome c, Nat. Cell Biol., 2, 645–652.

    Article  CAS  PubMed  Google Scholar 

  29. Blackburn, R. V., Galoforo, S. S., Berns, C. M., Armour, E. P., McEachern, D., Corry, P. M., and Lee, Y. J. (1997) Comparison of tumor growth between hsp25and hsp27transfected murine L929 cells in nude mice, Int. J. Cancer, 72, 871–877.

    Article  CAS  PubMed  Google Scholar 

  30. Tian, X., Zhao, L., Song, X., Yan, Y., Liu, N., Li, T., Yan, B., and Liu, B. (2016) HSP27 inhibits homocysteineinduced endothelial apoptosis by modulation of ROS production and mitochondrial caspase-dependent apoptotic pathway, BioMed Res. Int., 4847874.

    Google Scholar 

  31. Dubin, R. A., Wawrousek, E. F., and Piatigorsky, J. (1989) Expression of the murine alpha B-crystallin gene is not restricted to the lens, Mol. Cell. Biol., 9, 1083–1091.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Delaye, M., and Tardieu, A. (1983) Short-range order of crystallin proteins accounts for eye lens transparency, Nature, 302, 415–417.

    Article  CAS  PubMed  Google Scholar 

  33. Bloemendal, H., De Jong, W., Jaenicke, R., Lubsen, N. H., Slingsby, C., and Tardieu, A. (2004) Ageing and vision: structure, stability and function of lens crystallins, Prog. Biophys. Mol. Biol., 86, 407–485.

    Article  CAS  PubMed  Google Scholar 

  34. Horwitz, J. (1992) Alpha-crystallin can function as a molecular chaperone, Proc. Natl. Acad. Sci. USA, 89, 10449–10453.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Braun, N., Zacharias, M., Peschek, J., Kastenmuller, A., Zou, J., Hanzlik, M., Haslbeck, M., Rappsilber, J., Buchner, J., and Weinkauf, S. (2011) Multiple molecular architectures of the eye lens chaperone aB-crystallin elucidated by a triple hybrid approach, Proc. Natl. Acad. Sci. USA, 108, 20491–20496.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Brady, J. P., Garland, D., Duglas-Tabor, Y., Robison, W. G., Groome, A., and Wawrousek, E. F. (1997) Targeted disruption of the mouse aA-crystallin gene induces cataract and cytoplasmic inclusion bodies containing the small heat shock protein aB-crystallin, Proc. Natl. Acad. Sci. USA, 94, 884–889.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Shiliaev, N. G., Selivanova, O. M., and Galzitskaya, O. V. (2016) Search for conserved amino acid residues of the acrystallin proteins of vertebrates, J. Bioinform. Comput. Biol., 14, 1641004.

    Article  CAS  Google Scholar 

  38. Kiss, A. J., Mirarefi, A. Y., Ramakrishnan, S., Zukoski, C. F., Devries, A. L., and Cheng, C.-H. C. (2004) Cold-stable eye lens crystallins of the Antarctic nototheniid toothfish Dissostichus mawsoni Norman, J. Exp. Biol., 207, 46334649.

    Article  CAS  Google Scholar 

  39. Peschek, J., Braun, N., Franzmann, T. M., Georgalis, Y., Haslbeck, M., Weinkauf, S., and Buchner, J. (2009) The eye lens chaperone a-crystallin forms defined globular assemblies, Proc. Natl. Acad. Sci. USA, 106, 13272–13277.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Bloemendal, H., and Groenewoud, G. (1981) One-step separation of the subunits of a-crystallin by chromatofocusing in 6 M urea, Anal. Biochem., 117, 327–329.

    Article  CAS  PubMed  Google Scholar 

  41. Groenen, P. J., Merck, K. B., De Jong, W. W., and Bloemendal, H. (1994) Structure and modifications of the junior chaperone alpha-crystallin. From lens transparency to molecular pathology, Eur. J. Biochem., 225, 1–19.

    Article  CAS  PubMed  Google Scholar 

  42. Srinivas, P., Narahari, A., Petrash, J. M., Swamy, M. J., and Reddy, G. B. (2010) Importance of eye lens a-crystallin heteropolymer with 3: 1 aA to aB ratio: stability, aggregation, and modifications, IUBMB Life, 62, 693–702.

    Article  CAS  PubMed  Google Scholar 

  43. Reddy, G. B., Kumar, P. A., and Kumar, M. S. (2006) Chaperone-like activity and hydrophobicity of alpha-crystallin, IUBMB Life, 58, 632–641.

    Article  CAS  PubMed  Google Scholar 

  44. Reddy, G. B., Das, K. P., Petrash, J. M., and Surewicz, W. K. (2000) Temperature-dependent chaperone activity and structural properties of human aAand aB-crystallins, J. Biol. Chem., 275, 4565–4570.

    Article  CAS  PubMed  Google Scholar 

  45. Haley, D. A., Horwitz, J., and Stewart, P. L. (1998) The small heat-shock protein, aB-crystallin, has a variable quaternary structure, J. Mol. Biol., 277, 27–35.

    CAS  Google Scholar 

  46. Haley, D. A., Bova, M. P., Huang, Q.-L., Mchaourab, H. S., and Stewart, P. L. (2000) Small heat-shock protein structures reveal a continuum from symmetric to variable assemblies, J. Mol. Biol., 298, 261–272.

    Article  CAS  PubMed  Google Scholar 

  47. Hanazono, Y., Takeda, K., Oka, T., Abe, T., Tomonari, T., Akiyama, N., Aikawa, Y., Yohda, M., and Miki, K. (2013) Nonequivalence observed for the 16-meric structure of a small heat shock protein, SpHsp16.0, from Schizosaccharomyces pombe, Structure, 21, 220–228.

    CAS  PubMed  Google Scholar 

  48. Bagneris, C., Bateman, O. A., Naylor, C. E., Cronin, N., Boelens, W. C., Keep, N. H., and Slingsby, C. (2009) Crystal structures of alpha-crystallin domain dimers of alpha B-crystallin and Hsp20, J. Mol. Biol., 392, 12421252.

    Article  CAS  Google Scholar 

  49. Weeks, S. D., Baranova, E. V., Heirbaut, M., Beelen, S., Shkumatov, A. V., Gusev, N. B., and Strelkov, S. V. (2014) Molecular structure and dynamics of the dimeric human small heat shock protein HSPB6, J. Struct. Biol., 185, 342354.

    Article  CAS  Google Scholar 

  50. Chang, Z., Primm, T. P., Jakana, J., Lee, I. H., Serysheva, I., Chiu, W., Gilbert, H. F., and Quiocho, F. A. (1996) Mycobacterium tuberculosis 16-kDa antigen (Hsp16.3) functions as an oligomeric structure in vitro to suppress thermal aggregation, J. Biol. Chem., 271, 7218–7223.

    Article  CAS  PubMed  Google Scholar 

  51. Lee, G. J. (1997) A small heat shock protein stably binds heat-denatured model substrates and can maintain a substrate in a folding-competent state, EMBO J., 16, 659–671.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ehrnsperger, M., Lilie, H., Gaestel, M., and Buchner, J. (1999) The dynamics of Hsp25 quaternary structure and function of different oligomeric species, J. Biol. Chem., 274, 14867–14874.

    Article  CAS  PubMed  Google Scholar 

  53. Behlke, J., Lutsch, G., Gaestel, M., and Bielka, H. (1991) Supramolecular structure of the recombinant murine small heat shock protein hsp25, FEBS Lett., 288, 119–122.

    Article  CAS  PubMed  Google Scholar 

  54. Hanazono, Y., Takeda, K., Yohda, M., and Miki, K. (2012) Structural studies on the oligomeric transition of a small heat shock protein, StHsp14.0, J. Mol. Biol., 422, 100108.

    Google Scholar 

  55. Takeda, K., Hayashi, T., Abe, T., Hirano, Y., Hanazono, Y., Yohda, M., and Miki, K. (2011) Dimer structure and conformational variability in the N-terminal region of an archaeal small heat shock protein, StHsp14.0, J. Struct. Biol., 174, 92–99.

    Article  CAS  PubMed  Google Scholar 

  56. Aquilina, J. A., Benesch, J. L. P., Bateman, O. A., Slingsby, C., and Robinson, C. V. (2003) Polydispersity of a mammalian chaperone: mass spectrometry reveals the population of oligomers in aB-crystallin, Proc. Natl. Acad. Sci. USA, 100, 10611–10616.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Haslbeck, M., Kastenmuller, A., Buchner, J., Weinkauf, S., and Braun, N. (2008) Structural dynamics of archaeal small heat shock proteins, J. Mol. Biol., 378, 362–374.

    Article  CAS  PubMed  Google Scholar 

  58. Kim, R., Kim, K. K., Yokota, H., and Kim, S.-H. (1998) Small heat shock protein of Methanococcus jannaschii, a hyperthermophile, Proc. Natl. Acad. Sci. USA, 95, 91299133.

    Google Scholar 

  59. Jehle, S., Vollmar, B. S., Bardiaux, B., Dove, K. K., Rajagopal, P., Gonen, T., Oschkinat, H., and Klevit, R. E. (2011) N-terminal domain of alphaB-crystallin provides a conformational switch for multimerization and structural heterogeneity, Proc. Natl. Acad. Sci. USA, 108, 6409–6414.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Jehle, S., Rajagopal, P., Bardiaux, B., Markovic, S., Kuhne, R., Stout, J. R., Higman, V. A., Klevit, R. E., Van Rossum, B.-J., and Oschkinat, H. (2010) Solid-state NMR and SAXS studies provide a structural basis for the activation of aB-crystallin oligomers, Nat. Struct. Mol. Biol., 17, 1037–1042.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Horwitz, J. (2009) Alpha crystallin: the quest for a homogeneous quaternary structure, Exp. Eye Res., 88, 190–194.

    Article  CAS  PubMed  Google Scholar 

  62. Baldwin, A. J., Hilton, G. R., Lioe, H., Bagneris, C., Benesch, J. L. P., and Kay, L. E. (2011) Quaternary dynamics of aB-crystallin as a direct consequence of localised tertiary fluctuations in the C-terminus, J. Mol. Biol., 413, 310320.

    Google Scholar 

  63. Cheng, G., Basha, E., Wysocki, V. H., and Vierling, E. (2008) Insights into small heat shock protein and substrate structure during chaperone action derived from hydrogen/deuterium exchange and mass spectrometry, J. Biol. Chem., 283, 26634–26642.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Jakob, U., Gaestel, M., Engel, K., and Buchner, J. (1993) Small heat shock proteins are molecular chaperones, J. Biol. Chem., 268, 1517–1520.

    CAS  PubMed  Google Scholar 

  65. Ehrnsperger, M., Graber, S., Gaestel, M., and Buchner, J. (1997) Binding of non-native protein to Hsp25 during heat shock creates a reservoir of folding intermediates for reactivation, EMBO J., 16, 221–229.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Ahrman, E., Gustavsson, N., Hultschig, C., Boelens, W. C., and Emanuelsson, C. S. (2007) Small heat shock proteins prevent aggregation of citrate synthase and bind to the N-terminal region which is absent in thermostable forms of citrate synthase, Extremophiles, 11, 659–666.

    Article  PubMed  CAS  Google Scholar 

  67. Basha, E., Friedrich, K. L., and Vierling, E. (2006) The Nterminal arm of small heat shock proteins is important for both chaperone activity and substrate specificity, J. Biol. Chem., 281, 39943–39952.

    Article  CAS  PubMed  Google Scholar 

  68. Jaya, N., Garcia, V., and Vierling, E. (2009) Substrate binding site flexibility of the small heat shock protein molecular chaperones, Proc. Natl. Acad. Sci. USA, 106, 15604–15609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Mchaourab, H. S., Godar, J. A., and Stewart, P. L. (2009) Structure and mechanism of protein stability sensors: the chaperone activity of small heat-shock proteins, Biochemistry, 48, 3828–3837.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Bepperling, A., Alte, F., Kriehuber, T., Braun, N., Weinkauf, S., Groll, M., Haslbeck, M., and Buchner, J. (2012) Alternative bacterial two-component small heat shock protein systems, Proc. Natl. Acad. Sci. USA, 109, 20407–20412.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Franzmann, T. M., Menhorn, P., Walter, S., and Buchner, J. (2008) Activation of the chaperone Hsp26 is controlled by the rearrangement of its thermosensor domain, Mol. Cell, 29, 207–216.

    Article  CAS  PubMed  Google Scholar 

  72. McDonald, E. T., Bortolus, M., Koteiche, H. A., and Mchaourab, H. S. (2012) Sequence, structure, and dynamic determinants of Hsp27 (HspB1) equilibrium dissociation are encoded by the N-terminal domain, Biochemistry, 51, 1257–1268.

    CAS  PubMed  Google Scholar 

  73. Iwaki, T., Kume- Iwaki, A., Liem, R. K., and Goldman, J. E. (1989) Alpha B-crystallin is expressed in non-lenticular tissues and accumulates in Alexander’s disease brain, Cell, 57, 71–78.

    Article  CAS  PubMed  Google Scholar 

  74. Renkawek, K., De Jong, W. W., Merck, K. B., Frenken, C. W., Van Workum, F. P., and Bosman, G. J. (1992) alpha-Bcrystallin is present in reactive glia in Creutzfeldt-Jakob disease, Acta Neuropathol. (Berl.), 83, 324–327.

    Article  CAS  Google Scholar 

  75. Oliveira, A. O., Osmand, A., Outeiro, T. F., Muchowski, P. J., and Finkbeiner, S. (2016) aB-Crystallin overexpression in astrocytes modulates the phenotype of the BACHD mouse model of Huntington’s disease, Hum. Mol. Genet., 25, 1677–1689.

    Article  CAS  PubMed  Google Scholar 

  76. Ecroyd, H., and Carver, J. A. (2009) Crystallin proteins and amyloid fibrils, Cell. Mol. Life Sci., 66, 62–81.

    Article  CAS  PubMed  Google Scholar 

  77. Renkawek, K., Voorter, C. E., Bosman, G. J., Van Workum, F. P., and De Jong, W. W (1994) Expression of aB-crystallin in Alzheimer’s disease, Acta Neuropathol. (Berl.), 87, 155160.

    Google Scholar 

  78. Benndorf, R., Martin, J. L., Kosakovsky Pond, S. L., and Wertheim, J. O. (2014) Neuropathyand myopathy-associated mutations in human small heat shock proteins: characteristics and evolutionary history of the mutation sites, Mutat. Res. Rev. Mutat. Res., doi: 10.1016/j.mrrev.2014.02.004.

  79. Peferoen, L. A. N., Gerritsen, W. H., Breur, M., Ummenthum, K. M. D., Peferoen- Baert, R. M. B., Van der Valk, P., Van Noort, J. M., and Amor, S. (2015) Small heat shock proteins are induced during multiple sclerosis lesion development in white but not grey matter, Acta Neuropathol. Commun., 3, 87.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Malin, D., Petrovic, V., Strekalova, E., Sharma, B., and Cryns, V. L. (2016) aB-crystallin: portrait of a malignant chaperone as a cancer therapeutic target, Pharmacol. Ther., 160, 1–10.

    Article  CAS  PubMed  Google Scholar 

  81. Delbecq, S. P., and Klevit, R. E. (2013) One size does not fit all: the oligomeric states of aB crystallin, FEBS Lett., 587, 1073–1080.

    Article  CAS  PubMed  Google Scholar 

  82. Mymrikov, E. V., Bukach, O. V., Seit- Nebi, A. S., and Gusev, N. B. (2010) The pivotal role of the beta 7 strand in the intersubunit contacts of different human small heat shock proteins, Cell Stress Chaperones, 15, 365–377.

    Article  CAS  PubMed  Google Scholar 

  83. Wang, K., Gawinowicz, M. A., and Spector, A. (2000) The effect of stress on the pattern of phosphorylation of alphaA and alphaB crystallin in the rat lens, Exp. Eye Res., 71, 385–393.

    Article  CAS  PubMed  Google Scholar 

  84. Bennardini, F., Wrzosek, A., and Chiesi, M. (1992) Alpha B-crystallin in cardiac tissue. Association with actin and desmin filaments, Circ. Res., 71, 288–294.

    Article  CAS  PubMed  Google Scholar 

  85. Lomiwes, D., Hurst, S. M., Dobbie, P., Frost, D. A., Hurst, R. D., Young, O. A., and Farouk, M. M. (2014) The protection of bovine skeletal myofibrils from proteolytic damage post mortem by small heat shock proteins, Meat Sci., 97, 548–557.

    Article  CAS  PubMed  Google Scholar 

  86. Huang, Y., Wang, Z., Liu, Y., Xiong, H., Zhao, Y., Wu, L., Yuan, C., Wang, L., Hou, Y., Yu, G., Huang, Z., Xu, C., Chen, Q., and Wang, Q. K. (2016) aB-crystallin interacts with Nav1.5 and regulates ubiquitination and internalization of cell surface Nav1.5, J. Biol. Chem., 291, 1103011041.

    Google Scholar 

  87. Gong, X., Ming, X., Deng, P., and Jiang, Y. (2010) Mechanisms regulating the nuclear translocation of p38 MAP kinase, J. Cell. Biochem., 110, 1420–1429.

    Article  CAS  PubMed  Google Scholar 

  88. Jin, J.-K., Whittaker, R., Glassy, M. S., Barlow, S. B., Gottlieb, R. A., and Glembotski, C. C. (2008) Localization of phosphorylated alpha B-crystallin to heart mitochondria during ischemia-reperfusion, Am. J. Physiol. Heart Circ. Physiol., 294, H337–344.

    Article  CAS  PubMed  Google Scholar 

  89. Shin, J.-H., Jeong, J.-Y., Jin, Y., Kim, I.-D., and Lee, J.K. (2011) p38ß MAPK affords cytoprotection against oxidative stress-induced astrocyte apoptosis via induction of aB-crystallin and its anti-apoptotic function, Neurosci. Lett., 501, 132–137.

    Article  CAS  PubMed  Google Scholar 

  90. Den Engelsman, J., Van de Schootbrugge, C., Yong, J., Pruijn, G. J. M., and Boelens, W. C. (2013) Pseudophosphorylated aB-crystallin is a nuclear chaperone imported into the nucleus with help of the SMN complex, PLoS One, 8, e73489.

    Article  CAS  Google Scholar 

  91. Nefedova, V. V., Muranova, L. K., Sudnitsyna, M. V., Ryzhavskaya, A. S., and Gusev, N. B. (2015) Small heat shock proteins and distal hereditary neuropathies, Biochemistry (Moscow), 80, 1734–1747.

    Article  CAS  Google Scholar 

  92. Bova, M. P., Yaron, O., Huang, Q., Ding, L., Haley, D. A., Stewart, P. L., and Horwitz, J. (1999) Mutation R120G in alpha B-crystallin, which is linked to a desmin-related myopathy, results in an irregular structure and defective chaperone-like function, Proc. Natl. Acad. Sci. USA, 96, 6137–6142.

    CAS  Google Scholar 

  93. Den Engelsman, J., Gerrits, D., De Jong, W. W., Robbins, J., Kato, K., and Boelens, W. C. (2005) Nuclear import of alpha-B-crystallin is phosphorylation-dependent and hampered by hyperphosphorylation of the myopathyrelated mutant R120G, J. Biol. Chem., 280, 37139–37148.

    Article  CAS  PubMed  Google Scholar 

  94. Mitra, A., Basak, T., Datta, K., Naskar, S., Sengupta, S., and Sarkar, S. (2013) Role of a-crystallin B as a regulatory switch in modulating cardiomyocyte apoptosis by mitochondria or endoplasmic reticulum during cardiac hypertrophy and myocardial infarction, Cell Death Dis., 4, e582.

    Article  CAS  Google Scholar 

  95. Mao, Y.-W., Liu, J.-P., Xiang, H., and Li, D. W.-C. (2004) Human alphaAand alphaB-crystallins bind to Bax and Bcl-X(S) to sequester their translocation during staurosporine-induced apoptosis, Cell Death Differ., 11, 512526.

    Article  CAS  Google Scholar 

  96. Chis, R., Sharma, P., Bousette, N., Miyake, T., Wilson, A., Backx, P. H., and Gramolini, A. O. (2012) a-Crystallin B prevents apoptosis after H2O2 exposure in mouse neonatal cardiomyocytes, Am. J. Physiol. Heart Circ. Physiol., 303, 967–978.

    Article  CAS  Google Scholar 

  97. Adhikari, A. S., Sridhar Rao, K., Rangaraj, N., Parnaik, V. K., and Mohan Rao, C. (2004) Heat stress-induced localization of small heat shock proteins in mouse myoblasts: intranuclear lamin A/C speckles as target for aB-crystallin and Hsp25, Exp. Cell Res., 299, 393–403.

    Article  CAS  PubMed  Google Scholar 

  98. Van Rijk, A. F., Stege, G. J., Bennink, E. J., May, A., and Bloemendal, H. (2003) Nuclear staining for the small heat shock protein aB-crystallin colocalizes with splicing factor SC35, Eur. J. Cell Biol., 82, 361–368.

    Article  PubMed  Google Scholar 

  99. Den Engelsman, J., Bennink, E. J., Doerwald, L., Onnekink, C., Wunderink, L., Andley, U. P., Kato, K., De Jong, W. W., and Boelens, W. C. (2004) Mimicking phosphorylation of the small heat-shock protein alphaB-crystallin recruits the F-box protein FBX4 to nuclear SC35 speckles, Eur. J. Biochem., 271, 4195–4203.

    Article  CAS  PubMed  Google Scholar 

  100. Ecroyd, H., and Carver, J. A. (2008) The effect of small molecules in modulating the chaperone activity of alphaBcrystallin against ordered and disordered protein aggregation, FEBS J., 275, 935–947.

    Article  CAS  PubMed  Google Scholar 

  101. Hochberg, G. K. A., Ecroyd, H., Liu, C., Cox, D., Cascio, D., Sawaya, M. R., Collier, M. P., Stroud, J., Carver, J. A., Baldwin, A. J., Robinson, C. V., Eisenberg, D. S., Benesch, J. L. P., and Laganowsky, A. (2014) The structured core domain of aB-crystallin can prevent amyloid fibrillation and associated toxicity, Proc. Natl. Acad. Sci. USA, 111, e1562-E1570.

    Article  CAS  Google Scholar 

  102. Posner, M., Hawke, M., LaCava, C., Prince, C. J., Bellanco, N. R., and Corbin, R. W. (2008) A proteome map of the zebrafish (Danio rerio) lens reveals similarities between zebrafish and mammalian crystallin expression, Mol. Vis., 14, 806–814.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Ghahghaei, A., Rekas, A., Carver, J. A., and Augusteyn, R. C. (2009) Structure/function studies of dogfish a-crystallin, comparison with bovine a-crystallin, Mol. Vis., 15, 2411–2420.

    CAS  Google Scholar 

  104. Horwitz, J., Bova, M. P., Ding, L. L., Haley, D. A., and Stewart, P. L. (1999) Lens alpha-crystallin: function and structure, Eye Lond. Engl., 13, 403–408.

    Google Scholar 

  105. Srinivas, P. N., Reddy, P. Y., and Reddy, G. B. (2008) Significance of alpha-crystallin heteropolymer with a 3: 1 alphaA/alphaB ratio: chaperone-like activity, structure and hydrophobicity, Biochem. J., 414, 453–460.

    CAS  PubMed  Google Scholar 

  106. Wei, J., Dobnikar, J., Curk, T., and Song, F. (2016) The effect of attractive interactions and macromolecular crowding on crystallins association, PLoS One, 11, e0151159.

    Google Scholar 

  107. Laganowsky, A., Benesch, J. L. P., Landau, M., Ding, L., Sawaya, M. R., Cascio, D., Huang, Q., Robinson, C. V., Horwitz, J., and Eisenberg, D. (2010) Crystal structures of truncated alphaA and alphaB crystallins reveal structural mechanisms of polydispersity important for eye lens function, Protein Sci. Publ. Protein Soc., 19, 1031–1043.

    Article  CAS  Google Scholar 

  108. Laganowsky, A., and Eisenberg, D. (2010) Non-3D domain swapped crystal structure of truncated zebrafish alphaA crystallin, Protein Sci. Publ. Protein Soc., 19, 1978–1984.

    Article  CAS  Google Scholar 

  109. Fan, Q., Huang, L.-Z., Zhu, X.-J., Zhang, K.-K., Ye, H.F., Luo, Y., Sun, X.-H., Zhou, P., and Lu, Y. (2014) Identification of proteins that interact with alpha A-crystallin using a human proteome microarray, Mol. Vis., 20, 117–124.

    PubMed  PubMed Central  Google Scholar 

  110. Costello, M. J., Brennan, L. A., Basu, S., Chauss, D., Mohamed, A., Gilliland, K. O., Johnsen, S., Menko, A. S., and Kantorow, M. (2013) Autophagy and mitophagy participate in ocular lens organelle degradation, Exp. Eye Res., 116, 141–150.

    Article  CAS  PubMed  Google Scholar 

  111. Rao, N. A., Saraswathy, S., Pararajasegaram, G., and Bhat, S. P. (2012) Small heat shock protein aA-crystallin prevents photoreceptor degeneration in experimental autoimmune uveitis, PLoS One, 7, e33582.

    Article  CAS  Google Scholar 

  112. Shiels, A., and Hejtmancik, J. F. (2016) Mutations and mechanisms in congenital and age-related cataracts, Exp. Eye Res., doi: 10.1016/j.exer.2016.06.011.

  113. Boncoraglio, A., Minoia, M., and Carra, S. (2012) The family of mammalian small heat shock proteins (HSPBs): implications in protein deposit diseases and motor neuropathies, Int. J. Biochem. Cell Biol., 44, 1657–1669.

    Article  CAS  PubMed  Google Scholar 

  114. Bhagyalaxmi, S. G., Srinivas, P., Barton, K. A., Kumar, K. R., Vidyavathi, M., Petrash, J. M., Bhanuprakash Reddy, G., and Padma, T. (2009) A novel mutation (F71L) in alphaA-crystallin with defective chaperone-like function associated with age-related cataract, Biochim. Biophys. Acta, 1792, 974–981.

    Article  CAS  PubMed  Google Scholar 

  115. Ramkumar, S., Thankappan, B., Fujii, N., Natarajaseenivasan, K., and Anbarasu, K. (2015) Interaction of aA-crystallin F71L mutant with wild type aAand aB-crystallins by mammalian two hybrid assay, Int. J. Biol. Macromol., 76, 102–108.

    Article  CAS  PubMed  Google Scholar 

  116. Tjondro, H. C., Xi, Y.-B., Chen, X.-J., Su, J.-T., and Yan, Y.-B. (2016) Membrane insertion of aA-crystallin is oligomer-size dependent, Biochem. Biophys. Res. Commun., 473, 1–7.

    Article  CAS  PubMed  Google Scholar 

  117. Gu, F., Luo, W., Li, X., Wang, Z., Lu, S., Zhang, M., Zhao, B., Zhu, S., Feng, S., Yan, Y., Huang, S., and Ma, X. (2008) A novel mutation in alpha-A-crystallin (CRYAA) caused autosomal dominant congenital cataract in a large Chinese family, Hum. Mutat., 29, 769.

    Article  PubMed  Google Scholar 

  118. Mackay, D. S., Andley, U. P., and Shiels, A. (2003) Cell death triggered by a novel mutation in the alpha-A-crystallin gene underlies autosomal dominant cataract linked to chromosome 21q, Eur. J. Hum. Genet., 11, 784–793.

    Article  CAS  PubMed  Google Scholar 

  119. Thampi, P., Hassan, A., Smith, J. B., and Abraham, E. C. (2002) Enhanced C-terminal truncation of alphaAand alphaB-crystallins in diabetic lenses, Invest. Ophthalmol. Vis. Sci., 43, 3265–3272.

    PubMed  Google Scholar 

  120. Banerjee, P. R., Pande, A., Shekhtman, A., and Pande, J. (2015) Molecular mechanism of the chaperone function of mini-a-crystallin, a 19-residue peptide of human a-crystallin, Biochemistry, 54, 505–515.

    CAS  Google Scholar 

  121. Raju, M., Santhoshkumar, P., Xie, L., and Sharma, K. K. (2014) Addition of aA-crystallin sequence 164-173 to a mini-chaperone DFVIFLDVKHFSPEDLT alters the conformation but not the chaperone-like activity, Biochemistry, 53, 2615–2623.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Lin, P. P., Barry, R. C., Smith, D. L., and Smith, J. B. (1998) In vivo acetylation identified at lysine 70 of human lens alphaA-crystallin, Protein Sci. Publ. Protein Soc., 7, 1451–1457.

    Article  CAS  Google Scholar 

  123. Nagaraj, R. H., Nahomi, R. B., Shanthakumar, S., Linetsky, M., Padmanabha, S., Pasupuleti, N., Wang, B., Santhoshkumar, P., Panda, A. K., and Biswas, A. (2012) Acetylation of aA-crystallin in the human lens: effects on structure and chaperone function, Biochim. Biophys. Acta, 1822, 120–129.

    Article  CAS  PubMed  Google Scholar 

  124. Fujii, N., Awakura, M., Takemoto, L., Inomata, M., Takata, T., Fujii, N., and Saito, T. (2003) Characterization of alphaA-crystallin from high molecular weight aggregates in the normal human lens, Mol. Vis., 9, 315–322.

    CAS  PubMed  Google Scholar 

  125. Takata, T., and Fujii, N. (2015) Effect of Asp 96 isomerization on the properties of a lens aB-crystallin-derived short peptide, J. Pharm. Biomed. Anal., 116, 139–144.

    Article  CAS  PubMed  Google Scholar 

  126. Takata, T., and Fujii, N. (2016) Isomerization of Asp residues plays an important role in aA-crystallin dissociation, FEBS J., 283, 850–859.

    Article  CAS  PubMed  Google Scholar 

  127. Takemoto, L. J. (1998) Quantitation of asparagine-101 deamidation from alpha-A crystallin during aging of the human lens, Curr. Eye Res., 17, 247–250.

    Article  CAS  PubMed  Google Scholar 

  128. Chaves, J. M., Srivastava, K., Gupta, R., and Srivastava, O. P. (2008) Structural and functional roles of deamidation and/or truncation of Nor C-termini in human alpha Acrystallin, Biochemistry, 47, 10069–10083.

    Article  CAS  PubMed  Google Scholar 

  129. Takemoto, L., and Emmons, T. (1991) Truncation of a Acrystallin from the human lens, Exp. Eye Res., 53, 811813.

    Article  Google Scholar 

  130. Lund, A. L., Smith, J. B., and Smith, D. L. (1996) Modifications of the water-insoluble human lens alphacrystallins, Exp. Eye Res., 63, 661–672.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Protein Research, Russian Academy of Sciences, 142290, Pushchino, Moscow Region, Russia

    T. S. Tikhomirova, O. M. Selivanova & O. V. Galzitskaya

  2. Institute for Biological Instrumentation, Russian Academy of Sciences, 142290, Pushchino, Moscow Region, Russia

    T. S. Tikhomirova

Authors
  1. T. S. Tikhomirova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. O. M. Selivanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. O. V. Galzitskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to O. V. Galzitskaya.

Additional information

Published in Russian in Biokhimiya, 2017, Vol. 82, No. 2, pp. 208-225.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tikhomirova, T.S., Selivanova, O.M. & Galzitskaya, O.V. α-Crystallins are small heat shock proteins: Functional and structural properties. Biochemistry Moscow 82, 106–121 (2017). https://doi.org/10.1134/S0006297917020031

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297917020031

Keywords

Search

Navigation