Biopolym. Cell. 2009; 25(5):372-383.
http://dx.doi.org/10.7124/bc.0007EF
Reviews
Hsp90 molecular chaperone: structure, functions and participation in the cardio-vascular pathologies
1Kroupskaya I. V.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680

Abstract

This review is devoted to analysis of structural and functional properties of molecular chaperon Hsp90. Hsp90 are highly widespread family of heat shock proteins . Protein is found in eubacteria and all branches of eukarya, but it is apparently absent in archaea. It is one of key regulators of numerous signalling pathways, cell growth and development, apoptosis, induction of autoimmunity and progression of heart failure. The full functional activity of Hsp90 shows up in a complex with other molecular chaperones and co-chaperones. Molecular interactions between chaperones, different signaling proteins and protein-partners are highly crucial for the normal functioning of signaling pathways and its destruction are causes the alteration of cell physiology up to its death.
Keywords: Hsp90, domain, structure, signaling pathways, apoptosis
Full text: (PDF, in English) (PDF, in Russian)

References

[1] Seckler R., Jaenicke R. Protein folding and protein refolding. FASEB J. 1992;6(8):2545-52.
[2] Ellis J. Proteins as molecular chaperones Nature 1987 328, N 6129:378–379.
[3] Versteeg S., Mogk A., Schumann W. The Bacillus subtilis htpG gene is not involved in thermal stress management Mol. Gen. Genet 1999 261, N 4:582–588.
[4] Prodromou C., Piper P. W., Pearl L. H. Expression and crystallisation of the yeast Hsp82 chaperone and preliminary Xray diffraction studies of the amino-terminal domain Proteins: Structure, Function, Genetics 1996 25, N 4:517– 522.
[5] Pearl L. H., Prodromou C. Structure and mechanism of the Hsp90 molecular chaperone machinery Annu. Rev. Biochem 2006 75:271–294.
[6] Obermann W. M. J., Sondermann H., Russo A. A., Pavletich N. P., Hartl F. U. In vivo function of Hsp90 is dependent on ATP binding and ATP hydrolysis J. Cell Biol 1998 143, N 4:901–910.
[7] Prodromou C., Roe S. M., Piper P. W., Pearl L. H. A molecular clamp in the crystal structure of the N-terminal domain of the yeast Hsp90 chaperone Nat. Struct. Biol 1997 4, N 2:477–482.
[8] Chavany C., Mimnaugh E., Miller P., Bitton R., Nguyen P. p185erbB2 binds to GRP94 in vivo J. Biol. Chem 1996 271, N 9:4974–4977.
[9] Prodromou C., Roe S. M., O'Brien R., Ladbury J. E., Piper P. W., Pearl L. H. Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone Cell 1997 90, N 1:65–75.
[10] Soldano K. L., Jivan A., Nicchitta C. V., Gewirth D. T. Structure of the N-terminal domain of GRP94 J. Biol. Chem 2003 278, N 48:48330–48338.
[11] Huai Q., Wang H. C., Liu Y. D., Kim H. Y., Toft D., Ke H. M. Structures of the N-terminal and middle domains of E. coli Hsp90 and conformation changes upon ADP binding Structure 2005 13, N 6:579–590.
[12] Meyer P., Prodromou C., Hu B., Vaughan C., Roe S. M., Panaretou B., Piper P. W., Pearl L. H. Structural and functional analysis of the middle segment of hsp90: implications for ATP hydrolysis and client protein and cochaperone interactions Mol. Cell 2003 11, N 3:647–658.
[13] Minami Y., Kimura Y., Kawasaki H., Suzuki K., Yahara I. The carboxy-terminal region of mammalian HSP90 is required for its dimerization and function in vivo Mol. Cell. Biol 1994 14, N 2:1459–1464.
[14] Harris S. F., Shiau A. K., Agard D. A. The crystal structure of the carboxy-terminal dimerization domain of htpG, the Escherichia coli Hsp90, reveals a potential substrate binding site Structure 2004 12, N 6:1087–1097.
[15] Prodromou C., Panaretou B., Chohan S., Siligardi G., O'Brien R., Ladbury J. E., Roe S. M., Piper P. W., Pearl L. H. The ATPase cycle of Hsp90 drives a molecular «clamp» via transient dimerization of the N-terminal domains The EMBO J 2000 19, N 16:4383–4392.
[16] Louvion J. F., Warth R., Picard D. Two eukaryote-specific regions of Hsp82 are dispensable for its viability and signal transduction functions in yeast Proc. Nat. Acad. Sci. USA 1996 93, N 24:13937–13942.
[17] Siligardi G., Hu B., Panaretou B., Piper P. W., Pearl L. H., Prodromou C. Co-chaperone regulation of conformational switching in the Hsp90 ATPase cycle J. Biol. Chem 2004 279, N 50:51989–51998.
[18] McLaughlin S. H., Ventouras L. A., Lobbezoo B., Jackson S. E. Independent ATPase activity of Hsp90 subunits creates a flexible assembly platform J. Mol. Biol 2004 344, N 3:813–826.
[19] Berger J. M., Gamblin S. J., Harrison S. C., Wang J. C. Structure and mechanism of DNA topoisomerase II Nature 1996 379, N 6562:225–232.
[20] Ban C., Junop M., Yang W. Transformation of MutL by ATP binding and hydrolysis: a switch in DNA mismatch repair Cell 1999 97, N 1:85–97.
[21] Young J. C., Hartl F. U. Polypeptide release by Hsp90 involves ATP hydrolysis and is enhanced by the co-chaperone p23 The EMBO J 2000 19, N 17:5930–5940.
[22] Soti C., Racz A., Csermely P. A nucleotide-dependent molecular switch controls ATP binding at the C-terminal domain of hsp90: N-terminal nucleotide binding unmasks a C-terminal binding pocket J. Biol. Chem 2002 277, N 9:7066–7075.
[23] Pratt W. B., Galigniana M. D., Harrell J. M., DeFranco D. B. Role of hsp90 and the hsp90-binding immunophilins in signalling protein movement Cell. Signal 2004 16, N 8:857–872.
[24] Perez-Terzic C., Gacy M. A., Bortolon R. Directed inhibition of nuclear import in cellular hypertrophy J. Biol. Chem 2001 276, N 23:20566–20571.
[25] Swynghedauw B. Molecular mechanisms of myocardial remodeling Physiol. Rev 1999 79, N 1:215–262.
[26] Schlatter H., Langer T., Rosmus S., Onneken M.-L., Fasold H. A novel function for the 90 kDa heat-shock protein (Hsp90): facilitating nuclear export of 60S ribosomal subunits Biochem. J 2002 362, N 3:675–684.
[27] Vittone M. B. A., Maraldi N. M. Cell stress and ribosome crystallization. J. Submicrosc. Cytol. Pathol.; 1995 27(2):199–207.
[28] Helmbrecht K., Zeise E., Rensing L. Chaperones in cell cycle regulation and mitogenic signal transduction: a review Cell Prolif 2000 33, N 6:341–365.
[29] Sato S., Fujita N., Tsuruo T. Modulation of Akt kinase activity by binding to Hsp90 Proc. Nat. Acad. Sci. USA 2000 97, N 20:10832–10837.
[30] Young J. C., Moarefi I., Hartl F. U. Hsp90: a specialized but essential protein-folding tool J. Cell Biol 2001 154, N 2:267–274.
[31] Imai J., Yahara I. Role of Hsp90 in salt stress tolerance via stabilization and regulation of calcineurin Mol. Cell. Biol 2000 20, N 24:9262–9270.
[32] Dittmar K. D., Banach M., Galigniana M. D., Pratt W. B. The role of DnaJ-like proteins in glucocorticoid receptor-hsp90 heterocomplex assembly by the reconstituted hsp90-p60hsp70 foldosome complex J. Biol. Chem 1998 273, N 13:7358–7366.
[33] Pratt W. B., Toft D. O. Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone machinery. Exp Biol Med (Maywood). 2003;228(2):111-33.
[34] Arbeitman M. N., Hogness D. S. Molecular chaperones activate the Drosophila ecdysone receptor, an RXR heterodimer Cell 2000 101, N 1:67–77.
[35] Zou J., Guo Y., Guettouche T., Smith D., Voellmy R. Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1 Cell 1998 94, N 4:471–480.
[36] DeFranco D. B., Madan A. P., Tang Y., Chandran U. R., Xiao N., Yang J. Nucleocytoplasmic shuttling of steroid receptors Vitam. Horm 1995 51:315–338.
[37] Davies T. H., Ning Y. M., Sanchez E. R. A new first step in activation of steroid receptors: hormone-induced switching of FKBP51 and FKBP52 immunophilins J. Biol. Chem 2002 277, N 7:4597–4600.
[38] Gorlich D., Kutay U. Transport between the cell nucleus and the cytoplasm Annu. Rev. Cell Biol 1999 15:607– 660.
[39] Hache R. J. G., Tse R., Reich T., Savory G. A., Lefebvre Y. A. Nucleocytoplasmic trafficking of steroid-free glucocorticoid receptor J. Biol. Chem 1999 274, N 3:1432–1439.
[40] Phair R. D., Misteli T. High mobility of proteins in the mammalian cell nucleus Nature 2000 404, N 3:604–609.
[41] Meier U. T., Blobel G. Nopp140 shuttles on tracks between nucleolus and cytoplasm Cell 1992 70, N 1:127–138.
[42] Czar M. J., Owens-Grillo J. K., Yem A. W. The hsp56 im munophilin component of untransformed steroid receptor complexes is localized both to microtubules in the cytoplasm and to the same nonrandom regions within the nucleus as the steroid receptor Mol. Endocrinol 1994 8, N 12:1731–1741.
[43] DeFranco D. B. Navigating steroid hormone receptors through the nuclear compartment Mol. Endocrinol 2002 16, N 7:1449–1455.
[44] Morishima Y., Kanelakis K. C., Murphy P. J. M., Lowe E. R., Jenkins G. J., Osawa Y., Sunahara R. K., Pratt W. B. The Hsp90 cochaperone p23 is the limiting component of the multiprotein Hsp90/Hsp70-based chaperone system in vivo where it acts to stabilize the client protein/Hsp90 complex J. Biol. Chem 2003 278, N 49:48754–48763.
[45] Meacham G. C., Patterson C., Zhang W., Younger J. M., Cyr D. M. The Hsc70 co-chaperone CHIP targets immature CFTR for proteasomal degradation Cell Biol 2001 3:100–105.
[46] Hohfeld J., Cyr D. M., Patterson C. From the cradle to the grave: molecular chaperones that may choose between folding and degradation EMBO Rep 2001 2, N 10:885– 890.
[47] Kim T-S., Jang C-Y., Kim H. D., Lee J. Y., Ahn B-Y., Kim J. Interaction of Hsp90 with ribosomal proteins protects from ubiquitination and proteasome-dependent degradation Mol. Biol. Cell 2006 17, N 2:824–833.
[48] Zaarur N., Gabai V. L., Porco J. A., Calderwood S., Sherman M. Y. Targeting heat shock response to sensitize cancer cells to proteasome and Hsp90 inhibitors Cancer Res 2006 66, N 31:783–791.
[49] Gabrielson K., Bedja D., Pin S., Tsao A., Gama L., Yuan B., Muratore N. Heat shock protein 90 and Erbb2 in the cardiac response to doxorubicin injury Cancer Res 2007 67, N 4:1436–1441.
[50] Rezzani R., Rodella L., Dessy C., Daneau G., Bianchi R., Feron O. Changes in HSP90 expression determine the effects of cyclosporine A on the NO pathway in rat myocardium FEBS Lett 2003 552, N 2–3:125–129.
[51] Kupatt C., Dessy C., Hinkel R., Raake P., Daneau G., Bouzin C., Boekstegers P., Feron O. Heat shock protein 90 transfection reduces ischemia-reperfusion-induced myocardial dysfunction via reciprocal endothelial NO synthase Serine 1177 phosphorylation and Threonine 495 dephosphorylation Arterioscler. Thromb. Vasc. Biol 2004 24, N 8:1435–1441.
[52] Yamaguchi O., Watanabe T., Nishida K., Kashiwase K., Higuchi Y., Takeda T., Hikoso S., Hirotani S., Asahi M., Otsu K. Cardiac-specific disruption of the c-raf-1 gene induces cardiac dysfunction and apoptosis J. Clin. Invest 2004 114, N 7:937–943.
[53] Nollen E. A. A., Morimoto R. I. Chaperoning signaling pathways: molecular chaperones as stress-sensing «heat shock» proteins J. Cell Sci 2002 115, N 14:2809–2816.
[54] Srikakulam R., Winkelmann D. A. Chaperone-mediated folding and assembly of myosin in striated muscle J. Cell Sci 2004 117, N 4:641–652.
[55] Nowotny M., Spiechowicz M., Jastrzebska B., Filipek A., Kitagawa K., Kuznicki J. Calcium-regulated interaction of Sgt1 with S100A6 (Calcyclin) and other S100 proteins J. Biol. Chem 2003 278, N 29:26923–26928
[56] Brancaccio M., Guazzone S., Menini N., Sibona E., Hirsch E., De Andrea M., Rocchi M., Altruda F., Tarone G., Silengo L. Melusin is a new muscle specific interactor for beta(1) integrin cytoplasmic domain J. Biol. Chem 1999 274, N 41:29282–29288.
[57] Michowski W., Lee Y-T., Chazin W. J., Kuznicki J. Melusin binds calcyclin (S100A6) protein in a Ca2+-dependent fashion Eur. J. Biochem 2003 1 Suppl., 1 July: Abstr. N P3.7–09.
[58] Sbroggib M., Ferretti R., Percivalle E., Gutkowska M., Zylicz A., Michowski W., Kuznicki J., Accornero F., Pacchioni B., Lanfranchi G., Hamm J., Turco E., Silengo L., Tarone G., Brancaccio M. The mammalian CHORD-containing protein melusin is a stress response protein interacting with Hsp90 and Sgt1 FEBS Lett 2008 582, N 13:1788–1794.
[59] Morimoto R. I. Dynamic remodeling of transcription complexes by molecular chaperones Cell 2002 110, N 3:281–284.
[60] Griffin T. M., Valdez T. V., Mestril R. Radicicol activates heat shock protein expression and cardioprotection in neonatal rat cardiomyocytes Amer. J. Physiol. Heart Circ. Physiol 2004 287, N 3:1081–1088.
[61] Ferdinandy P., Schulz R. Nitric oxide, superoxide, and peroxynitrite in myocardial ischaemia–reperfusion injury and preconditioning Brit. J. Pharmacol 2003 138, N 4:532–543.