Alpha-crystallin can function as a molecular chaperone.
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Journal: 1992/December - Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
PUBMED: 1438232
Abstract:
The alpha-crystallins (alpha A and alpha B) are major lens structural proteins of the vertebrate eye that are related to the small heat shock protein family. In addition, crystallins (especially alpha B) are found in many cells and organs outside the lens, and alpha B is overexpressed in several neurological disorders and in cell lines under stress conditions. Here I show that alpha-crystallin can function as a molecular chaperone. Stoichiometric amounts of alpha A and alpha B suppress thermally induced aggregation of various enzymes. In particular, alpha-crystallin is very efficient in suppressing the thermally induced aggregation of beta- and gamma-crystallins, the two other major mammalian structural lens proteins. alpha-Crystallin was also effective in preventing aggregation and in refolding guanidine hydrochloride-denatured gamma-crystallin, as judged by circular dichroism spectroscopy. My results thus indicate that alpha-crystallin refracts light and protects proteins from aggregation in the transparent eye lens and that in nonlens cells alpha-crystallin may have other functions in addition to its capacity to suppress aggregation of proteins.
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Proc Natl Acad Sci U S A 89(21): 10449-10453
PMID: 1438232

Alpha-crystallin can function as a molecular chaperone.

Abstract

The alpha-crystallins (alpha A and alpha B) are major lens structural proteins of the vertebrate eye that are related to the small heat shock protein family. In addition, crystallins (especially alpha B) are found in many cells and organs outside the lens, and alpha B is overexpressed in several neurological disorders and in cell lines under stress conditions. Here I show that alpha-crystallin can function as a molecular chaperone. Stoichiometric amounts of alpha A and alpha B suppress thermally induced aggregation of various enzymes. In particular, alpha-crystallin is very efficient in suppressing the thermally induced aggregation of beta- and gamma-crystallins, the two other major mammalian structural lens proteins. alpha-Crystallin was also effective in preventing aggregation and in refolding guanidine hydrochloride-denatured gamma-crystallin, as judged by circular dichroism spectroscopy. My results thus indicate that alpha-crystallin refracts light and protects proteins from aggregation in the transparent eye lens and that in nonlens cells alpha-crystallin may have other functions in addition to its capacity to suppress aggregation of proteins.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Ingolia TD, Craig EA. Four small Drosophila heat shock proteins are related to each other and to mammalian alpha-crystallin. Proc Natl Acad Sci U S A. 1982 Apr;79(7):2360–2364.[PMC free article] [PubMed] [Google Scholar]
  • Nene V, Dunne DW, Johnson KS, Taylor DW, Cordingley JS. Sequence and expression of a major egg antigen from Schistosoma mansoni. Homologies to heat shock proteins and alpha-crystallins. Mol Biochem Parasitol. 1986 Nov;21(2):179–188. [PubMed] [Google Scholar]
  • de Jong WW, Leunissen JA, Leenen PJ, Zweers A, Versteeg M. Dogfish alpha-crystallin sequences. Comparison with small heat shock proteins and Schistosoma egg antigen. J Biol Chem. 1988 Apr 15;263(11):5141–5149. [PubMed] [Google Scholar]
  • Moscona AA, Fox L, Smith J, Degenstein L. Antiserum to lens antigens immunostains Müller glia cells in the neural retina. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5570–5573.[PMC free article] [PubMed] [Google Scholar]
  • Lewis GP, Erickson PA, Kaska DD, Fisher SK. An immunocytochemical comparison of Müller cells and astrocytes in the cat retina. Exp Eye Res. 1988 Dec;47(6):839–853. [PubMed] [Google Scholar]
  • Bhat SP, Nagineni CN. alpha B subunit of lens-specific protein alpha-crystallin is present in other ocular and non-ocular tissues. Biochem Biophys Res Commun. 1989 Jan 16;158(1):319–325. [PubMed] [Google Scholar]
  • Dubin RA, Wawrousek EF, Piatigorsky J. Expression of the murine alpha B-crystallin gene is not restricted to the lens. Mol Cell Biol. 1989 Mar;9(3):1083–1091.[PMC free article] [PubMed] [Google Scholar]
  • Iwaki T, Kume-Iwaki A, Liem RK, Goldman JE. Alpha B-crystallin is expressed in non-lenticular tissues and accumulates in Alexander's disease brain. Cell. 1989 Apr 7;57(1):71–78. [PubMed] [Google Scholar]
  • Lowe J, Landon M, Pike I, Spendlove I, McDermott H, Mayer RJ. Dementia with beta-amyloid deposition: involvement of alpha B-crystallin supports two main diseases. Lancet. 1990 Aug 25;336(8713):515–516. [PubMed] [Google Scholar]
  • Renkawek K, de Jong WW, Merck KB, Frenken CW, van Workum FP, Bosman GJ. alpha B-crystallin is present in reactive glia in Creutzfeldt-Jakob disease. Acta Neuropathol. 1992;83(3):324–327. [PubMed] [Google Scholar]
  • Duguid JR, Rohwer RG, Seed B. Isolation of cDNAs of scrapie-modulated RNAs by subtractive hybridization of a cDNA library. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5738–5742.[PMC free article] [PubMed] [Google Scholar]
  • Klemenz R, Fröhli E, Aoyama A, Hoffmann S, Simpson RJ, Moritz RL, Schäfer R. Alpha B crystallin accumulation is a specific response to Ha-ras and v-mos oncogene expression in mouse NIH 3T3 fibroblasts. Mol Cell Biol. 1991 Feb;11(2):803–812.[PMC free article] [PubMed] [Google Scholar]
  • Murano S, Thweatt R, Shmookler Reis RJ, Jones RA, Moerman EJ, Goldstein S. Diverse gene sequences are overexpressed in werner syndrome fibroblasts undergoing premature replicative senescence. Mol Cell Biol. 1991 Aug;11(8):3905–3914.[PMC free article] [PubMed] [Google Scholar]
  • Klemenz R, Fröhli E, Steiger RH, Schäfer R, Aoyama A. Alpha B-crystallin is a small heat shock protein. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3652–3656.[PMC free article] [PubMed] [Google Scholar]
  • Dasgupta S, Hohman TC, Carper D. Hypertonic stress induces alpha B-crystallin expression. Exp Eye Res. 1992 Mar;54(3):461–470. [PubMed] [Google Scholar]
  • Kato K, Shinohara H, Kurobe N, Goto S, Inaguma Y, Ohshima K. Immunoreactive alpha A crystallin in rat non-lenticular tissues detected with a sensitive immunoassay method. Biochim Biophys Acta. 1991 Oct 25;1080(2):173–180. [PubMed] [Google Scholar]
  • Buchner J, Schmidt M, Fuchs M, Jaenicke R, Rudolph R, Schmid FX, Kiefhaber T. GroE facilitates refolding of citrate synthase by suppressing aggregation. Biochemistry. 1991 Feb 12;30(6):1586–1591. [PubMed] [Google Scholar]
  • Höll-Neugebauer B, Rudolph R, Schmidt M, Buchner J. Reconstitution of a heat shock effect in vitro: influence of GroE on the thermal aggregation of alpha-glucosidase from yeast. Biochemistry. 1991 Dec 17;30(50):11609–11614. [PubMed] [Google Scholar]
  • Walsh MT, Sen AC, Chakrabarti B. Micellar subunit assembly in a three-layer model of oligomeric alpha-crystallin. J Biol Chem. 1991 Oct 25;266(30):20079–20084. [PubMed] [Google Scholar]
  • Horwitz J, Kabasawa I, Kinoshita JH. Conformation of gamma-crystallins of the calf lens: effects of temperature and denaturing agents. Exp Eye Res. 1977 Aug;25(2):199–208. [PubMed] [Google Scholar]
  • Mandal K, Chakrabarti B, Thomson J, Siezen RJ. Structure and stability of gamma-crystallins. Denaturation and proteolysis behavior. J Biol Chem. 1987 Jun 15;262(17):8096–8102. [PubMed] [Google Scholar]
  • Maiti M, Kono M, Chakrabarti B. Heat-induced changes in the conformation of alpha- and beta-crystallins: unique thermal stability of alpha-crystallin. FEBS Lett. 1988 Aug 15;236(1):109–114. [PubMed] [Google Scholar]
  • Steadman BL, Trautman PA, Lawson EQ, Raymond MJ, Mood DA, Thomson JA, Middaugh CR. A differential scanning calorimetric study of the bovine lens crystallins. Biochemistry. 1989 Dec 12;28(25):9653–9658. [PubMed] [Google Scholar]
  • Castoro JA, Bettelheim FA. Thermal denaturation of alpha-crystallin. Lens Eye Toxic Res. 1989;6(4):781–793. [PubMed] [Google Scholar]
  • Chiou SH, Azari P. Physicochemical characterization of alpha-crystallins from bovine lenses: hydrodynamic and conformational properties. J Protein Chem. 1989 Feb;8(1):1–17. [PubMed] [Google Scholar]
  • McFall-Ngai MJ, Horwitz J. A comparative study of the thermal stability of the vertebrate eye lens: Antarctic ice fish to the desert iguana. Exp Eye Res. 1990 Jun;50(6):703–709. [PubMed] [Google Scholar]
  • Blundell T, Lindley P, Miller L, Moss D, Slingsby C, Tickle I, Turnell B, Wistow G. The molecular structure and stability of the eye lens: x-ray analysis of gamma-crystallin II. Nature. 1981 Feb 26;289(5800):771–777. [PubMed] [Google Scholar]
  • Ellis RJ, van der Vies SM. Molecular chaperones. Annu Rev Biochem. 1991;60:321–347. [PubMed] [Google Scholar]
  • Wickner W, Driessen AJ, Hartl FU. The enzymology of protein translocation across the Escherichia coli plasma membrane. Annu Rev Biochem. 1991;60:101–124. [PubMed] [Google Scholar]
  • Gething MJ, Sambrook J. Protein folding in the cell. Nature. 1992 Jan 2;355(6355):33–45. [PubMed] [Google Scholar]
  • Langer T, Lu C, Echols H, Flanagan J, Hayer MK, Hartl FU. Successive action of DnaK, DnaJ and GroEL along the pathway of chaperone-mediated protein folding. Nature. 1992 Apr 23;356(6371):683–689. [PubMed] [Google Scholar]
  • Thomson JA, Augusteyn RC. On the structure of alpha-crystallin: construction of hybrid molecules and homopolymers. Biochim Biophys Acta. 1989 Feb 23;994(3):246–252. [PubMed] [Google Scholar]
  • Tardieu A, Laporte D, Licinio P, Krop B, Delaye M. Calf lens alpha-crystallin quaternary structure. A three-layer tetrahedral model. J Mol Biol. 1986 Dec 20;192(4):711–724. [PubMed] [Google Scholar]
  • Van Der Ouderaa FJ, De Jong WW, Hilderink A, Bloemendal H. The amino-acids sequence of the alphaB2 chain of bovine alpha-crystallin. Eur J Biochem. 1974 Nov 1;49(1):157–168. [PubMed] [Google Scholar]
  • Piatigorsky J, O'Brien WE, Norman BL, Kalumuck K, Wistow GJ, Borras T, Nickerson JM, Wawrousek EF. Gene sharing by delta-crystallin and argininosuccinate lyase. Proc Natl Acad Sci U S A. 1988 May;85(10):3479–3483.[PMC free article] [PubMed] [Google Scholar]
  • Piatigorsky J. Lens crystallins. Innovation associated with changes in gene regulation. J Biol Chem. 1992 Mar 5;267(7):4277–4280. [PubMed] [Google Scholar]
  • Benedek GB, Chylack LT, Jr, Libondi T, Magnante P, Pennett M. Quantitative detection of the molecular changes associated with early cataractogenesis in the living human lens using quasielastic light scattering. Curr Eye Res. 1987 Dec;6(12):1421–1432. [PubMed] [Google Scholar]
  • Pauli D, Tonka CH, Tissieres A, Arrigo AP. Tissue-specific expression of the heat shock protein HSP27 during Drosophila melanogaster development. J Cell Biol. 1990 Sep;111(3):817–828.[PMC free article] [PubMed] [Google Scholar]
  • Kato K, Shinohara H, Goto S, Inaguma Y, Morishita R, Asano T. Copurification of small heat shock protein with alpha B crystallin from human skeletal muscle. J Biol Chem. 1992 Apr 15;267(11):7718–7725. [PubMed] [Google Scholar]
  • Spector A, Chiesa R, Sredy J, Garner W. cAMP-dependent phosphorylation of bovine lens alpha-crystallin. Proc Natl Acad Sci U S A. 1985 Jul;82(14):4712–4716.[PMC free article] [PubMed] [Google Scholar]
  • Voorter CE, Mulders JW, Bloemendal H, de Jong WW. Some aspects of the phosphorylation of alpha-crystallin A. Eur J Biochem. 1986 Oct 1;160(1):203–210. [PubMed] [Google Scholar]
  • Chiesa R, Gawinowicz-Kolks MA, Kleiman NJ, Spector A. Definition and comparison of the phosphorylation sites of the A and B chains of bovine alpha-crystallin. Exp Eye Res. 1988 Feb;46(2):199–208. [PubMed] [Google Scholar]
  • Hoenders HJ, Bloemendal H. The N-terminus of the lens protein alpha-crystallin. Biochim Biophys Acta. 1967 Sep 19;147(1):183–185. [PubMed] [Google Scholar]
  • de Jong WW, van Kleef FS, Bloemendal H. Intracellular carboxy-terminal degradation of the alpha A chain of alpha-crystallin. Eur J Biochem. 1974 Oct 1;48(1):271–276. [PubMed] [Google Scholar]
  • van Kleef FS, Nijzink-Maas MJ, Hoenders HJ. Intracellular degradation of alpha-crystallin. Fractionation and characterization of degraded alpha A-chains. Eur J Biochem. 1974 Oct 2;48(2):563–570. [PubMed] [Google Scholar]
  • Voorter CE, Roersma ES, Bloemendal H, de Jong WW. Age-dependent deamidation of chicken alpha A-crystallin. FEBS Lett. 1987 Sep 14;221(2):249–252. [PubMed] [Google Scholar]
  • Roquemore EP, Dell A, Morris HR, Panico M, Reason AJ, Savoy LA, Wistow GJ, Zigler JS, Jr, Earles BJ, Hart GW. Vertebrate lens alpha-crystallins are modified by O-linked N-acetylglucosamine. J Biol Chem. 1992 Jan 5;267(1):555–563. [PubMed] [Google Scholar]
  • Sherman MYu, Goldberg AL. Heat shock in Escherichia coli alters the protein-binding properties of the chaperonin groEL by inducing its phosphorylation. Nature. 1992 May 14;357(6374):167–169. [PubMed] [Google Scholar]
Jules Stein Eye Institute, University of California, Los Angeles School of Medicine 90024-7008.
Jules Stein Eye Institute, University of California, Los Angeles School of Medicine 90024-7008.
Copyright notice
Abstract
The alpha-crystallins (alpha A and alpha B) are major lens structural proteins of the vertebrate eye that are related to the small heat shock protein family. In addition, crystallins (especially alpha B) are found in many cells and organs outside the lens, and alpha B is overexpressed in several neurological disorders and in cell lines under stress conditions. Here I show that alpha-crystallin can function as a molecular chaperone. Stoichiometric amounts of alpha A and alpha B suppress thermally induced aggregation of various enzymes. In particular, alpha-crystallin is very efficient in suppressing the thermally induced aggregation of beta- and gamma-crystallins, the two other major mammalian structural lens proteins. alpha-Crystallin was also effective in preventing aggregation and in refolding guanidine hydrochloride-denatured gamma-crystallin, as judged by circular dichroism spectroscopy. My results thus indicate that alpha-crystallin refracts light and protects proteins from aggregation in the transparent eye lens and that in nonlens cells alpha-crystallin may have other functions in addition to its capacity to suppress aggregation of proteins.
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