This was the first study to show that skeletal muscle sarcomeric proteins of the titin family (X-, C-, and H-proteins) can form in vitro amyloid aggregates of different types: granular aggregates, protofibrils, helically twisted ribbons, linear fibrils, and bundles of linear fibrils. The amyloid nature of these aggregates was confirmed by electron, polarization, and fluorescence microscopy and by spectral methods. In contrast to other amyloidogenic proteins, the X-, C-, and H-proteins easily form amyloids under mild conditions close to physiological ones with respect to pH, ionic strength, and temperature. Similarly to amyloid fibrils of the -peptide and tau protein in Alzheimer's disease, amyloid aggregates formed by the X-, C-, and H-proteins are destroyed by the antibiotic tetracycline. Thus, the new proteins—precursors of amyloids and possible participants of amyloidoses in muscles—were discovered. Further study of in vitro amyloidogenesis of these proteins would help to find approaches to controlling this process in organs and tissues.

References

1. S. Y. Tan and M. B. Perys, Amyloidosis 25, 403–414 (1994).
2. V. N. Uversky and A. L. Fink, Biochim. Biophys. Acta 1698, 131–153 (2004).
3. M. R. N. Krebs, E. H. C. Bromley, and A. M. Donald, J. Struct. Biol. 149, 30–37 (2005).
4. W. E. Klunk, J. W. Pettergrew, and D. J. Abraham, J. Histochem. Cytochem. 37, 1273–1281 (1989).
5. H. Naiki, K. Higuchi, M. Hosokawa, and T. Takeda, Anal. Biochem. 177, 244–249 (1989).
6. H. LeVine III, Protein Sci. 2, 404–410 (1993).
7. M. Goedert, Nature Rev. Neurosci 2, 492–501 (2001).
8. C. M. Dobson, Phil. Trans. Roy. Soc., Ser. B 356, 133–145 (2001).
9. S. B. Prusiner, Proc. Natl. Acad. Sci. USA 95, 13363–13383 (1998).
10. G. S. Jackson and A. R. Clarke, Curr. Opin. Struct. Biol. 10, 69–74 (2000).
11. N. A. Freidina, A. A. Orlova, and Z. A. Podlubnaya, Structural Bases of Regulation of Biological Motility, Ed. by G. R. Ivanitskii (Nauka, Moscow, 1980) [in Russian].
12. P. Bennet, R. Starr, A. Elliot, and G. Offer, J. Mol. Biol. 184, 297–309 (1985).
13. Z. A. Podlubnaya, Structure and Function of Proteins of Contractile Systems, Ed. by G. P. Pinaev (Nauka, Leningrad, 1987), pp. 71–90 [in Russian].
14. K. Yamamoto and K. Moss, J. Biol. Chem. 258, 8395–8401 (1983).
15. R. Starr and G. Offer, J. Mol. Biol. 170, 675–698 (1983).
16. P. M. Bennet, D. O. Furst, and M. Gautel, Rev. Physiol. Biochem. Pharmacol. 138, 203–234.
17. I. M. Vikhlyantsev and Z. A. Podlubnaya, Biofizika 48, 499–504 (2003).
18. G. Offer, C. Moos, and R. Starr, J. Mol. Biol. 74, 653–676 (1973).
19. J. D. Fritz, D. R. Swartz, and M. L. Greaser, Anal. Biochem. 180, 205–210 (1989).
20. H. Laemmli, Nature 227, 680–685 (1970).
21. R. Starr and G. Offer, Methods Enzymol., Part B 85, 130–138 (1982).
22. C. S. Goldsbury, S. Wirtz, S. Sunderji, et al., J. Struct. Biol. 130, 217–231 (2000).
23. B. O'Nuallain, A. D. Williams, P. Westermark, and R. Wetzel, J. Biol. Chem. 279, 17490–17499 (2004).
24. F. Chiti, P. Webster, N. Taddei, et al., Proc. Natl. Acad. Sci. USA 96, 3590–3594 (1999).
25. J. W. Kelly, Curr. Opin. Struct. Biol. 8, 101–106 (1998).
26. H. LeVine III, Amyloid 2, 1–6 (1995).
27. Yu. A. Alekseeva, M. D. Shpigina, I. M. Vikhlyantsev, et al., Horizons of Biophysics: from Theory to Practice, Ed. by G. R. Ivanitskii (Pushchino, 2003), p. 83 [in Russian].
28. L. G. Marsagishvili, I. M. Vikhlyantsev, M. D. Shpagina, et al., in Proceeding of XVII Winter Youth Scientific School “Prospective Directions of Physicochemical Biology and Biotechnology” (Moscow, 2005), p. 7 [in Russian].
29. L. Marsagishvili, M. Shpagina, V. Emelyanenko, and Z. Podlubnaya, FEBS Journal 272, 297 (2005).
30. G. Forloni, L. Colombo, L. Girola, et al., FEBS Lett. 487, 404–407 (2001).