Human myocytes are protected from titin aggregation-induced stiffening by small heat shock proteins

Journal of Cell Biology

Volumn 204, Issue 2, 2014, Pages 187-202

  Kötter, Sebastian ^a   Unger, Andreas ^a   Hamdani, Nazha ^a   Lang, Patrick ^a   Vorgerd, Matthias ^b   Nagel Steger, Luitgard ^c   Linke, Wolfgang A ^a  

^a RUHR UNIVERSITY BOCHUM   (Germany)

^b RUHR UNIVERSITY BOCHUM   (Germany)

^c HEINRICH HEINE UNIVERSITY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA CRYSTALLIN; CONNECTIN; GLUTAMIC ACID; HEAT SHOCK PROTEIN 27; IMMUNOGLOBULIN; ISOPROTEIN; LYSINE; MONOMER; PROLINE; SMALL HEAT SHOCK PROTEIN; VALINE;

ACTIN FILAMENT; ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BINDING ASSAY; BINDING SITE; CELL PROTECTION; CONTROLLED STUDY; GEL PERMEATION CHROMATOGRAPHY; HEART MUSCLE CELL; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOFLUORESCENCE; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; LIGHT SCATTERING; MUSCLE FIBRIL; NONHUMAN; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN EXPRESSION; PROTEIN UNFOLDING; RABBIT; RAT; RIGIDITY; SARCOMERE; SEDIMENTATION RATE; TWO HYBRID SYSTEM; WILD TYPE;

ALPHA-CRYSTALLIN B CHAIN; ANIMALS; CONNECTIN; HSP27 HEAT-SHOCK PROTEINS; HUMANS; MUSCLE FIBERS, SKELETAL; MYOCYTES, CARDIAC; MYOFIBRILS; PROTEIN STRUCTURE, TERTIARY; RATS; STRESS, PHYSIOLOGICAL;

EID: 84892863880     PISSN: 00219525     EISSN: 15408140     Source Type: Journal    
DOI: 10.1083/jcb.201306077     Document Type: Article

References (76)

1. Bang, M.L., T. Centner, F. Fornoff, A.J. Geach, M. Gotthardt, M. McNabb, C.C. Witt, D. Labeit, C.C. Gregorio, H. Granzier, and S. Labeit. 2001. The complete gene sequence of titin, expression of an unusual approximately 700-kDa titin isoform, and its interaction with obscurin identify a novel Z-line to I-band linking system. Circ. Res. 89:1065-1072. http://dx.doi .org/10.1161/hh2301.100981
2. Barbato, R., R. Menabò, P. Dainese, E. Carafoli, S. Schiaffino, and F. Di Lisa. 1996. Binding of cytosolic proteins to myofibrils in ischemic rat hearts. Circ. Res. 78:821-828. http://dx.doi.org/10.1161/01.RES.78.5.821
3. Benjamin, I.J., and D.R. McMillan. 1998. Stress (heat shock) proteins: molecular chaperones in cardiovascular biology and disease. Circ. Res. 83:117-132. http://dx.doi.org/10.1161/01.RES.83.2.117
4. Bennardini, F., A. Wrzosek, and M. Chiesi. 1992. Alpha B-crystallin in cardiac tissue. Association with actin and desmin filaments. Circ. Res. 71:288-294. http://dx.doi.org/10.1161/01.RES.71.2.288
5. Berger, D.S., S.K. Fellner, K.A. Robinson, K. Vlasica, I.E. Godoy, and S.G. Shroff. 1999. Disparate effects of three types of extracellular acidosis on left ventricular function. Am. J. Physiol. 276:H582-H594.
6. Bullard, B., C. Ferguson, A. Minajeva, M.C. Leake, M. Gautel, D. Labeit, L. Ding, S. Labeit, J. Horwitz, K.R. Leonard, and W.A. Linke. 2004. Association of the chaperone alphaB-crystallin with titin in heart muscle. J. Biol. Chem. 279:7917-7924. http://dx.doi.org/10.1074/jbc.M307473200
7. Chernik, I.S., O.O. Panasenko, Y. Li, S.B. Marston, and N.B. Gusev. 2004. pH-induced changes of the structure of small heat shock proteins with molecular mass 24/27 kDa (HspB1). Biochem. Biophys. Res. Commun. 324:1199-1203. http://dx.doi.org/10.1016/j.bbrc.2004.09.176
8. da Silva Lopes, K., A. Pietas, M.H. Radke, and M. Gotthardt. 2011. Titin visualization in real time reveals an unexpected level of mobility within and between sarcomeres. J. Cell Biol. 193:785-798. http://dx.doi.org/ 10.1083/jcb.201010099
9. Dohke, T., A. Wada, T. Isono, M. Fujii, T. Yamamoto, T. Tsutamoto, and M. Horie. 2006. Proteomic analysis reveals significant alternations of cardiac small heat shock protein expression in congestive heart failure. J. Card. Fail. 12:77-84. http://dx.doi.org/10.1016/j.cardfail.2005.07.006
10. Donlin, L.T., C. Andresen, S. Just, E. Rudensky, C.T. Pappas, M. Kruger, E.Y. Jacobs, A. Unger, A. Zieseniss, M.W. Dobenecker, et al. 2012. Smyd2 controls cytoplasmic lysine methylation of Hsp90 and myofilament organization. Genes Dev. 26:114-119. http://dx.doi.org/10.1101/gad.177758.111
11. Doran, P., J. Gannon, K. O'Connell, and K. Ohlendieck. 2007. Aging skeletal muscle shows a drastic increase in the small heat shock proteins alphaBcrystallin/ HspB5 and cvHsp/HspB7. Eur. J. Cell Biol. 86:629-640. http://dx.doi.org/10.1016/j.ejcb.2007.07.003
12. Ehrnsperger, M., H. Lilie, M. Gaestel, and J. Buchner. 1999. The dynamics of Hsp25 quaternary structure. Structure and function of different oligomeric species. J. Biol. Chem. 274:14867-14874. http://dx.doi.org/10.1074/jbc.274.21.14867
13. Fischer, D., J. Matten, J. Reimann, C. Bönnemann, and R. Schröder. 2002. Expression, localization and functional divergence of alphaB-crystallin and heat shock protein 27 in core myopathies and neurogenic atrophy. Acta Neuropathol. 104:297-304.
14. Fu, L., and J.J. Liang. 2003. Enhanced stability of alpha B-crystallin in the presence of small heat shock protein Hsp27. Biochem. Biophys. Res. Commun. 302:710-714. http://dx.doi.org/10.1016/S0006-291X(03)00257-2
15. Golenhofen, N., P. Htun, W. Ness, R. Koob, W. Schaper, and D. Drenckhahn. 1999. Binding of the stress protein alpha B-crystallin to cardiac myofibrils correlates with the degree of myocardial damage during ischemia/ reperfusion in vivo. J. Mol. Cell. Cardiol. 31:569-580. http://dx.doi .org/10.1006/jmcc.1998.0892
16. Golenhofen, N., A. Arbeiter, R. Koob, and D. Drenckhahn. 2002. Ischemiainduced association of the stress protein alpha B-crystallin with I-band portion of cardiac titin. J. Mol. Cell. Cardiol. 34:309-319. http://dx.doi .org/10.1006/jmcc.2001.1513
17. Golenhofen, N., M.D. Perng, R.A. Quinlan, and D. Drenckhahn. 2004. Comparison of the small heat shock proteins alphaB-crystallin, MKBP, HSP25, HSP20, and cvHSP in heart and skeletal muscle. Histochem. Cell Biol. 122:415-425. http://dx.doi.org/10.1007/s00418-004-0711-z
18. Golenhofen, N., A. Redel, E.F. Wawrousek, and D. Drenckhahn. 2006. Ischemiainduced increase of stiffness of alphaB-crystallin/HSPB2-deficient myocardium. Pflugers Arch. 451:518-525. http://dx.doi.org/10.1007/ s00424-005-1488-1
19. Hamdani, N., J. Krysiak, M.M. Kreusser, S. Neef, C.G. Dos Remedios, L.S. Maier, M. Krüger, J. Backs, and W.A. Linke. 2013. Crucial role for Ca2(+)/calmodulin-dependent protein kinase-II in regulating diastolic stress of normal and failing hearts via titin phosphorylation. Circ. Res. 112:664-674. http://dx.doi.org/10.1161/CIRCRESAHA.111.300105
20. Hegyi, H., and P. Tompa. 2008. Intrinsically disordered proteins display no preference for chaperone binding in vivo. PLOS Comput. Biol. 4:e1000017. http://dx.doi.org/10.1371/journal.pcbi.1000017
21. Houmeida, A., A. Baron, J. Keen, G.N. Khan, P.J. Knight, W.F. Stafford III, K. Thirumurugan, B. Thompson, L. Tskhovrebova, and J. Trinick. 2008. Evidence for the oligomeric state of 'elastic' titin in muscle sarcomeres. J. Mol. Biol. 384:299-312. http://dx.doi.org/10.1016/j.jmb.2008.09.030
22. Inaguma, Y., K. Hasegawa, S. Goto, H. Ito, and K. Kato. 1995. Induction of the synthesis of hsp27 and alpha B crystallin in tissues of heat-stressed rats and its suppression by ethanol or an alpha 1-adrenergic antagonist. J. Biochem. 117:1238-1243.
23. Khong, T.K., D.J. McIntyre, G.A. Sagnella, N.D. Markandu, M.A. Miller, E.H. Baker, J.R. Griffiths, and G.A. MacGregor. 2001. In-vivo intracellular pH at rest and during exercise in patients with essential hypertension. J. Hypertens. 19:1595-1600. http://dx.doi.org/10.1097/00004872-200109000-00011
24. Kienitz, M.C., K. Bender, R. Dermietzel, L. Pott, and G. Zoidl. 2011. Pannexin 1 constitutes the large conductance cation channel of cardiac myocytes. J. Biol. Chem. 286:290-298. http://dx.doi.org/10.1074/jbc.M110.163477
25. Klemenz, R., A.C. Andres, E. Fröhli, R. Schäfer, and A. Aoyama. 1993. Expression of the murine small heat shock proteins hsp 25 and alpha B crystallin in the absence of stress. J. Cell Biol. 120:639-645. http://dx.doi .org/10.1083/jcb.120.3.639
26. Kley, R.A., P. Serdaroglu-Oflazer, Y. Leber, Z. Odgerel, P.F. van der Ven, M. Olivé, I. Ferrer, A. Onipe, M. Mihaylov, J.M. Bilbao, et al. 2012. Pathophysiology of protein aggregation and extended phenotyping in filaminopathy. Brain. 135:2642-2660. http://dx.doi.org/10.1093/brain/aws200
27. Knowlton, A.A., S. Kapadia, G. Torre-Amione, J.B. Durand, R. Bies, J. Young, and D.L. Mann. 1998. Differential expression of heat shock proteins in normal and failing human hearts. J. Mol. Cell. Cardiol. 30:811-818. http://dx.doi.org/10.1006/jmcc.1998.0646
28. Krüger, M., C. Sachse, W.H. Zimmermann, T. Eschenhagen, S. Klede, and W.A. Linke. 2008. Thyroid hormone regulates developmental titin isoform transitions via the phosphatidylinositol-3-kinase/AKT pathway. Circ. Res. 102:439-447. http://dx.doi.org/10.1161/CIRCRESAHA .107.162719
29. Lange, S., D. Auerbach, P. McLoughlin, E. Perriard, B.W. Schäfer, J.C. Perriard, and E. Ehler. 2002. Subcellular targeting of metabolic enzymes to titin in heart muscle may be mediated by DRAL/FHL-2. J. Cell Sci. 115:4925-4936. http://dx.doi.org/10.1242/jcs.00181
30. Larkins, N.T., R.M. Murphy, and G.D. Lamb. 2012. Absolute amounts and diffusibility of HSP72, HSP25, and αB-crystallin in fast-and slow-twitch skeletal muscle fibers of rat. Am. J. Physiol. Cell Physiol. 302:C228-C239. http://dx.doi.org/10.1152/ajpcell.00266.2011
31. Leake, M.C., D. Wilson, M. Gautel, and R.M. Simmons. 2004. The elasticity of single titin molecules using a two-bead optical tweezers assay. Biophys. J. 87:1112-1135. http://dx.doi.org/10.1529/biophysj.103.033571
32. Leake, M.C., A. Grützner, M. Krüger, and W.A. Linke. 2006. Mechanical properties of cardiac titin's N2B-region by single-molecule atomic force spectroscopy. J. Struct. Biol. 155:263-272. http://dx.doi.org/10.1016/j.jsb.2006.02.017
33. Li, H., W.A. Linke, A.F. Oberhauser, M. Carrion-Vazquez, J.G. Kerkvliet, H. Lu, P.E. Marszalek, and J.M. Fernandez. 2002. Reverse engineering of the giant muscle protein titin. Nature. 418:998-1002. http://dx.doi .org/10.1038/nature00938
34. Li, W., R. Rong, S. Zhao, X. Zhu, K. Zhang, X. Xiong, X. Yu, Q. Cui, S. Li, L. Chen, et al. 2012. Proteomic analysis of metabolic, cytoskeletal and stress response proteins in human heart failure. J. Cell. Mol. Med. 16:59-71. http://dx.doi.org/10.1111/j.1582-4934.2011.01336.x
35. Linding, R., J. Schymkowitz, F. Rousseau, F. Diella, and L. Serrano. 2004. A comparative study of the relationship between protein structure and beta-aggregation in globular and intrinsically disordered proteins. J. Mol. Biol. 342:345-353. http://dx.doi.org/10.1016/j.jmb.2004.06.088
36. Linke, W.A., and A. Grützner. 2008. Pulling single molecules of titin by AFM-recent advances and physiological implications. Pflugers Arch. 456:101-115. http://dx.doi.org/10.1007/s00424-007-0389-x
37. Linke, W.A., and M. Krüger. 2010. The giant protein titin as an integrator of myocyte signaling pathways. Physiology (Bethesda). 25:186-198. http:// dx.doi.org/10.1152/physiol.00005.2010
38. Linke, W.A., M. Ivemeyer, P. Mundel, M.R. Stockmeier, and B. Kolmerer. 1998. Nature of PEVK-titin elasticity in skeletal muscle. Proc. Natl. Acad. Sci. USA. 95:8052-8057. http://dx.doi.org/10.1073/pnas.95.14.8052
39. Linke, W.A., D.E. Rudy, T. Centner, M. Gautel, C. Witt, S. Labeit, and C.C. Gregorio. 1999. I-band titin in cardiac muscle is a three-element molecular spring and is critical for maintaining thin filament structure. J. Cell Biol. 146:631-644. http://dx.doi.org/10.1083/jcb.146.3.631
40. Liu, Y., and J.M. Steinacker. 2001. Changes in skeletal muscle heat shock proteins: pathological significance. Front. Biosci. 6:D12-D25. http://dx.doi .org/10.2741/Liu
41. Lu, X.Y., L. Chen, X.L. Cai, and H.T. Yang. 2008. Overexpression of heat shock protein 27 protects against ischaemia/reperfusion-induced cardiac dysfunction via stabilization of troponin I and T. Cardiovasc. Res. 79:500-508. http://dx.doi.org/10.1093/cvr/cvn091
42. Lutsch, G., R. Vetter, U. Offhauss, M. Wieske, H.J. Gröne, R. Klemenz, I. Schimke, J. Stahl, and R. Benndorf. 1997. Abundance and location of the small heat shock proteins HSP25 and alphaB-crystallin in rat and human heart. Circulation. 96:3466-3476. http://dx.doi.org/10.1161/01.CIR.96.10.3466
43. Marchetti, S., F. Sbrana, R. Raccis, L. Lanzi, C.M. Gambi, M. Vassalli, B. Tiribilli, A. Pacini, and A. Toscano. 2008. Dynamic light scattering and atomic force microscopy imaging on fragments of beta-connectin from human cardiac muscle. Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 77:021910. http://dx.doi.org/10.1103/PhysRevE.77.021910
44. Markov, D.I., A.V. Pivovarova, I.S. Chernik, N.B. Gusev, and D.I. Levitsky. 2008. Small heat shock protein Hsp27 protects myosin S1 from heat-induced aggregation, but not from thermal denaturation and ATPase inactivation. FEBS Lett. 582:1407-1412. http://dx.doi.org/10.1016/j.febslet.2008.03.035
45. Martin, J., T. Langer, R. Boteva, A. Schramel, A.L. Horwich, and F.U. Hartl. 1991. Chaperonin-mediated protein folding at the surface of groEL through a 'molten globule'-like intermediate. Nature. 352:36-42. http:// dx.doi.org/10.1038/352036a0
46. Martin, J.L., R. Mestril, R. Hilal-Dandan, L.L. Brunton, and W.H. Dillmann. 1997. Small heat shock proteins and protection against ischemic injury in cardiac myocytes. Circulation. 96:4343-4348. http://dx.doi.org/10.1161/01 .CIR.96.12.4343
47. Melkani, G.C., A. Cammarato, and S.I. Bernstein. 2006. alphaB-crystallin maintains skeletal muscle myosin enzymatic activity and prevents its aggregation under heat-shock stress. J. Mol. Biol. 358:635-645. http://dx.doi .org/10.1016/j.jmb.2006.02.043
48. Minajeva, A., M. Kulke, J.M. Fernandez, and W.A. Linke. 2001. Unfolding of titin domains explains the viscoelastic behavior of skeletal myofibrils. Biophys. J. 80:1442-1451. http://dx.doi.org/10.1016/S0006-3495(01)76116-4
49. Miyake, S., Y. Ishii, T. Watari, Z. Huang, and T. Tsuchiya. 2003. The influences of L(+)-lactate and pH on contractile performance in rabbit glycerinated skeletal muscle. Jpn. J. Physiol. 53:401-409. http://dx.doi.org/ 10.2170/jjphysiol.53.401
50. Monsellier, E., and F. Chiti. 2007. Prevention of amyloid-like aggregation as a driving force of protein evolution. EMBO Rep. 8:737-742. http://dx.doi .org/10.1038/sj.embor.7401034
51. Morton, J.P., A.C. Kayani, A. McArdle, and B. Drust. 2009. The exercise-induced stress response of skeletal muscle, with specific emphasis on humans. Sports Med. 39:643-662. http://dx.doi.org/10.2165/00007256-200939080-00003
52. Mymrikov, E.V., A.S. Seit-Nebi, and N.B. Gusev. 2011. Large potentials of small heat shock proteins. Physiol. Rev. 91:1123-1159. http://dx.doi .org/10.1152/physrev.00023.2010
53. Neagoe, C., M. Kulke, F. del Monte, J.K. Gwathmey, P.P. de Tombe, R.J. Hajjar, and W.A. Linke. 2002. Titin isoform switch in ischemic human heart disease. Circulation. 106:1333-1341. http://dx.doi.org/10.1161/01.CIR .0000029803.93022.93
54. Olsson, M.C., M. Krüger, L.H. Meyer, L. Ahnlund, L. Gransberg, W.A. Linke, and L. Larsson. 2006. Fibre type-specific increase in passive muscle tension in spinal cord-injured subjects with spasticity. J. Physiol. 577:339-352. http://dx.doi.org/10.1113/jphysiol.2006.116749
55. Opitz, C.A., M.C. Leake, I. Makarenko, V. Benes, and W.A. Linke. 2004. Developmentally regulated switching of titin size alters myofibrillar stiffness in the perinatal heart. Circ. Res. 94:967-975. http://dx.doi .org/10.1161/01.RES.0000124301.48193.E1
56. Orchard, C.H., and J.C. Kentish. 1990. Effects of changes of pH on the contractile function of cardiac muscle. Am. J. Physiol. 258:C967-C981.
57. Paulsen, G., F. Lauritzen, M.L. Bayer, J.M. Kalhovde, I. Ugelstad, S.G. Owe, J. Hallén, L.H. Bergersen, and T. Raastad. 2009. Subcellular movement and expression of HSP27, alphaB-crystallin, and HSP70 after two bouts of eccentric exercise in humans. J. Appl. Physiol. 107:570-582. http:// dx.doi.org/10.1152/japplphysiol.00209.2009
58. Pinz, I., J. Robbins, N.S. Rajasekaran, I.J. Benjamin, and J.S. Ingwall. 2008. Unmasking different mechanical and energetic roles for the small heat shock proteins CryAB and HSPB2 using genetically modified mouse hearts. FASEB J. 22:84-92. http://dx.doi.org/10.1096/fj.07-8130com
59. Rief, M., M. Gautel, F. Oesterhelt, J.M. Fernandez, and H.E. Gaub. 1997. Reversible unfolding of individual titin immunoglobulin domains by AFM. Science. 276:1109-1112. http://dx.doi.org/10.1126/science.276 .5315.1109
60. Sheikh, F., A. Raskin, P.H. Chu, S. Lange, A.A. Domenighetti, M. Zheng, X. Liang, T. Zhang, T. Yajima, Y. Gu, et al. 2008. An FHL1-containing complex within the cardiomyocyte sarcomere mediates hypertrophic biomechanical stress responses in mice. J. Clin. Invest. 118:3870-3880. (published erratum appears in J. Clin. Invest. 2012. 122:1584. http:// dx.doi.org/10.1172/JCI34472
61. Singh, B.N., K.S. Rao, T. Ramakrishna, N. Rangaraj, and ChM. Rao. 2007. Association of alphaB-crystallin, a small heat shock protein, with actin: role in modulating actin filament dynamics in vivo. J. Mol. Biol. 366:756-767. http://dx.doi.org/10.1016/j.jmb.2006.12.012
62. Somkuti, J., Z. Mártonfalvi, M.S. Kellermayer, and L. Smeller. 2013. Different pressure-temperature behavior of the structured and unstructured regions of titin. Biochim. Biophys. Acta. 1834:112-118. http://dx.doi.org/ 10.1016/j.bbapap.2012.10.001
63. Sun, Y., and T.H. MacRae. 2005. Small heat shock proteins: molecular structure and chaperone function. Cell. Mol. Life Sci. 62:2460-2476. http://dx.doi .org/10.1007/s00018-005-5190-4
64. Tskhovrebova, L., and J. Trinick. 1997. Direct visualization of extensibility in isolated titin molecules. J. Mol. Biol. 265:100-106. http://dx.doi .org/10.1006/jmbi.1996.0717
65. Tucker, N.R., and E.A. Shelden. 2009. Hsp27 associates with the titin filament system in heat-shocked zebrafish cardiomyocytes. Exp. Cell Res. 315:3176-3186. http://dx.doi.org/10.1016/j.yexcr.2009.06.030
66. Ulbricht, A., F.J. Eppler, V.E. Tapia, P.F. van der Ven, N. Hampe, N. Hersch, P. Vakeel, D. Stadel, A. Haas, P. Saftig, et al. 2013. Cellular mechanotransduction relies on tension-induced and chaperone-assisted autophagy. Curr. Biol. 23:430-435. http://dx.doi.org/10.1016/j.cub.2013.01.064
67. van de Klundert, F.A., M.L. Gijsen, P.R. van den Ijssel, L.H. Snoeckx, and W.W. de Jong. 1998. alpha B-crystallin and hsp25 in neonatal cardiac cells-differences in cellular localization under stress conditions. Eur. J. Cell Biol. 75:38-45. http://dx.doi.org/10.1016/S0171-9335(98)80044-7
68. Vaughan-Jones, R.D., K.W. Spitzer, and P. Swietach. 2009. Intracellular pH regulation in heart. J. Mol. Cell. Cardiol. 46:318-331. http://dx.doi.org/ 10.1016/j.yjmcc.2008.10.024
69. Verschuure, P., Y. Croes, P.R. van den Ijssel, R.A. Quinlan, W.W. de Jong, and W.C. Boelens. 2002. Translocation of small heat shock proteins to the actin cytoskeleton upon proteasomal inhibition. J. Mol. Cell. Cardiol. 34:117-128. http://dx.doi.org/10.1006/jmcc.2001.1493
70. Vicart, P.A., A. Caron, P. Guicheney, Z. Li, M.C. Prévost, A. Faure, D. Chateau, F. Chapon, F. Tomé, J.M. Dupret, et al. 1998. A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy. Nat. Genet. 20:92-95. http://dx.doi.org/10.1038/1765
71. Wang, X., R. Klevitsky, W. Huang, J. Glasford, F. Li, and J. Robbins. 2003. AlphaBcrystallin modulates protein aggregation of abnormal desmin. Circ. Res. 93:998-1005. http://dx.doi.org/10.1161/01.RES.0000102401.77712.ED
72. Willis, M.S., and C. Patterson. 2010. Hold me tight: Role of the heat shock protein family of chaperones in cardiac disease. Circulation. 122:1740-1751. http://dx.doi.org/10.1161/CIRCULATIONAHA.110.942250
73. Witt, C.C., B. Gerull, M.J. Davies, T. Centner, W.A. Linke, and L. Thierfelder. 2001. Hypercontractile properties of cardiac muscle fibers in a knockin mouse model of cardiac myosin-binding protein-C. J. Biol. Chem. 276:5353-5359. http://dx.doi.org/10.1074/jbc.M008691200
74. Wright, C.F., S.A. Teichmann, J. Clarke, and C.M. Dobson. 2005. The importance of sequence diversity in the aggregation and evolution of proteins. Nature. 438:878-881. http://dx.doi.org/10.1038/nature04195
75. Yoshida, K., T. Aki, K. Harada, K.M. Shama, Y. Kamoda, A. Suzuki, and S. Ohno. 1999. Translocation of HSP27 and MKBP in ischemic heart. Cell Struct. Funct. 24:181-185. http://dx.doi.org/10.1247/csf.24.181
76. Zhu, Y., J. Bogomolovas, S. Labeit, and H. Granzier. 2009. Single molecule force spectroscopy of the cardiac titin N2B element: effects of the molecular chaperone alphaB-crystallin with disease-causing mutations. J. Biol. Chem. 284:13914-13923. http://dx.doi.org/10.1074/jbc.M809743200