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Dimerization of Tropomyosins

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Tropomyosin

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 644))

Abstract

Tropomyosins consist of nearly 100% α-helix and assemble into parallel dimeric coiled-coils. Nonmuscle as well as muscle tropomyosins can form homodimers, however, expression of both muscle α and β tropomyosin subunits results in the preferential formation of stable α/β heterodimers in native muscle. The assembly preference of the muscle tropomyosin heterodimer can be understood in terms of its thermodynamically favorable energy distribution that provides increased stability over the homodimer. The simultaneous expression of multiple tropomyosin isoforms in nonmuscle cells (at least up to seven individual chains), however, points towards a more complex principle for determining dimer preference. The information for homoand hetero dimerization is contained within the tropomyosin molecule itself and the parameters for dimer selectivity are conferred in part by the alternatively spliced exons. However, it remains to be established if low molecular weight tropomyosin isoforms in nonmuscle cells engage in both homdimer and heterodimer formation in vivo. A thorough understanding of the selective dimer formation of the more than 40 tropomyosin isoforms is required to explain how subtle alterations in the sequence of one tropomyosin chain can result in the progression of diverse disease phenotypes.

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References

  1. Leavis PC, Gergely J. Thin filament proteins and thin filament-linked regulation of vertebrate muscle contraction. CRC Crit Rev Biochem 1984; 16:235–305.

    Article  PubMed  CAS  Google Scholar 

  2. Gunning PW, Shevzov G, Kee AJ et al. Tropomyosin isoforms: divining rods for actin cytoskeleton function. Trends Cell Biol 2005; 15:333–41.

    Article  PubMed  CAS  Google Scholar 

  3. Goodwin LO, Lees-Miller JP, Cheley S et al. Four fibroblast tropomyosin isoforms are expressed from the rat alpha-tropomyosin gene via alternative RNA splicing and the use of two promoters. J Biol Chem 1991; 266:8408–15.

    PubMed  CAS  Google Scholar 

  4. Lees-Miller JP, Helfman DM. The molecular basis for tropomyosin isoform diversity. Bioessays 1991; 13:429–37.

    Article  PubMed  CAS  Google Scholar 

  5. Pittenger MF, Kazzaz JA, Helfman DM. Functional properties of nonmuscle tropomyosin isoforms. Curr Opin Cell Biol 1994; 6:96–104.

    Article  PubMed  CAS  Google Scholar 

  6. Nyakern-Meazza M, Narayan K, Schutt CE et al. Tropomyosin and gelsolin cooperate in controlling the microfilament system. J Biol Chem 2002; 277:28774–9.

    Article  PubMed  CAS  Google Scholar 

  7. Bryce NC, Shevzov G, Ferguson V et al. Specification of actin filament function and molecular composition by tropomyosin isoforms. Mol Biol Cell 2003; 14:1002–16.

    Article  PubMed  CAS  Google Scholar 

  8. Schevzov G, Bryce NS, Almonte-Baldonado R et al. Specific features of neuronal size and shape are regulated by tropomyosin isoforms. Mol Biol Cell 2005; 16:3425–37.

    Article  PubMed  CAS  Google Scholar 

  9. Hillberg L, Zhao Rathje LS, Nyakern-Meazza M et al. Tropomyosins are present in lamellipodia of motile cells. Eur J Cell Biol 2006; 85:399–409.

    Article  PubMed  CAS  Google Scholar 

  10. Graceffa P. In-register homodimers of smooth muscle tropomyosin. Biochemistry 1989; 28:1282–7.

    Article  PubMed  CAS  Google Scholar 

  11. Whitby FG, Kent H, Stewart F et al. Structure of tropomyosin at 9 angstroms resolution. J Mol Biol 1992; 227:441–52.

    Article  PubMed  CAS  Google Scholar 

  12. Sanders C, Burtnick LD, Smillie LB. Native chicken gizzard tropomyosin is predominantly a beta gamma-heterodimer. J Biol Chem 1986; 261:12774–8.

    PubMed  CAS  Google Scholar 

  13. Lehrer SS, Qian Y, Hvidt S. Assembly of the native heterodimer of Rana esculenta tropomyosin by chain exchange. Science 1989; 246:926–8.

    Article  PubMed  CAS  Google Scholar 

  14. Laing NG, Wilton SD, Akkari PA et al. A mutation in the alpha tropomyosin gene TPM3 associated with autosomal dominant nemaline myopathy NEM1. Nat Genet 1995; 10:249.

    PubMed  CAS  Google Scholar 

  15. Corbett MA, Akkari PA, Domazetovska A et al. An α-Tropomyosin mutation alters dimer preference in nemaline myopathy. Ann Neurol 2005; 57:42–9.

    Article  PubMed  CAS  Google Scholar 

  16. Gimona M, Watakabe A, Helfman DM. Specificity of dimer formation in tropomyosins: influence of alternatively spliced exons on homodimer and heterodimer assembly. Proc Natl Acad Sci USA 1995; 92:9776–80.

    Article  PubMed  CAS  Google Scholar 

  17. Temm-Grove CJ, Guo W, Helfman DM. Low molecular weight rat fibroblast tropomyosin 5 (TM-5): cDNA cloning, actin-binding, localization and coiledcoil interactions. Cell Motil Cytoskeleton 1996; 33:223–40.

    Article  PubMed  CAS  Google Scholar 

  18. Araya E, Berthier C, Kim E et al. Regulation of coiled-coil assembly in tropomyosins. J Struct Biol 2002; 137:176–83.

    Article  PubMed  CAS  Google Scholar 

  19. Pittenger MF, Helfman DM. In vitro and in vivo characterization of four fibroblast tropomyosins produced in bacteria: TM-2, TM-3 TM-5a and TM-5b are colocalized in interphase fibroblasts. J Cell Biol 1992; 118:841–58.

    Article  PubMed  CAS  Google Scholar 

  20. Brown HR, Schachat FH. Renaturation of skeletal muscle tropomyosin: implications for in vivo assembly. Proc Natl Acad Sci USA 1985; 82:2359–63.

    Article  PubMed  CAS  Google Scholar 

  21. Lehrer SS, Qian Y. Unfolding/refolding studies of smooth muscle tropomyosin. Evidence for a chain exchange mechanism in the preferential assembly of the native heterodimer. J Biol Chem 1990; 265:1134–8.

    PubMed  CAS  Google Scholar 

  22. Matsumura F, Yamashiro-Matsumura S. Purification and characterization of multiple isoforms of tropomyosin from rat cultured cells. J Biol Chem 1985; 260:13851–9.

    PubMed  CAS  Google Scholar 

  23. Matsumura F, Yamashiro-Matsumura S. Purification and characterization of multiple isoforms of tropomyosin from rat cultured cells. J Biol Chem 1985; 260:13851–9.

    PubMed  CAS  Google Scholar 

  24. Kee AJ, Schevzov, G, Nair-Shalliker V et al. Sorting of a nonmuscle tropomyosin to a novel cytoskeletal compartment in skeletal muscle results in muscular dystrophy. J Cell Biol 2004; 166:685–96.

    Article  PubMed  CAS  Google Scholar 

  25. Cho YJ, Hitchcock-DeGregori SE. Relationship between alternatively spliced exons and functional domains in tropomyosin. Proc Natl Acad Sci USA 1991; 88:10153–57.

    Article  PubMed  CAS  Google Scholar 

  26. Censullo R, Cheung HC Tropomyosin length and two-stranded F-actin flexibility in the thin filament. J Mol Biol 1994; 243:520–9.

    Article  PubMed  CAS  Google Scholar 

  27. Coulton A, Lehrer SS, Geeves MA. Functional homodimers and heterodimers of recombinant smooth muscle tropomyosin. Biochemistry 2006; 45:12853–8.

    Article  PubMed  CAS  Google Scholar 

  28. Lehrer SS, Stafford WF 3rd. Preferential assembly of the tropomyosin heterodimer: equilibrium studies. Biochemistry 1991; 30:5682–8.

    Article  PubMed  CAS  Google Scholar 

  29. Brown JH, Kim K-H, Jun G et al. Deciphering the design of the tropomyosin molecule. Proc Natl Acad Sci USA 2001; 98:8496–501.

    Article  PubMed  CAS  Google Scholar 

  30. Lehrer SS, Quian Y. Unfolding/refolding studies of smooth muscle tropomyosin. J Biol Chem 1990; 265:1134–8.

    PubMed  CAS  Google Scholar 

  31. Kammerer RA, Schulthess T, Landwehr R et al. An autonomous folding unit mediates the assembly of two stranded coiled coils. Proc Natl Acad Sci USA 1998; 95:13419–24.

    Article  PubMed  CAS  Google Scholar 

  32. Lupas A, van Dyke M, Stock J. Predicting coiled coils from protein sequences. Science 1991; 252:1162–64.

    Article  CAS  Google Scholar 

  33. Wolf E, Kim PS, Berger B. MultiCoil: a program for predicting two-and three-stranded coiled coils. Protein Sci 1997; 6:1179–89.

    Article  PubMed  CAS  Google Scholar 

  34. Liu J, Rost B. Comparing function and structure between entire proteomes. Protein Sci 2001; 10:1970–9.

    Article  PubMed  CAS  Google Scholar 

  35. Ishii Y, Hitchcock-DeGregori SE, Mabuchi K et al. Unfolding domains of recombinant fusion alpha alpha-tropomyosin. Protein Sci 1992; 1:1319–25.

    Article  PubMed  CAS  Google Scholar 

  36. Jancsò A, Graceffa P. Smooth muscle tropomyosin coiled-coil dimers. Subunit composition, assembly and end-to-end interaction. J Biol Chem 1991; 266:5891–7.

    PubMed  Google Scholar 

  37. Lee DL, Lavigne P, Hodges RS. Are trigger sequences essential in the folding of two-stranded α-helical coiled-coils? J Mol Biol 2001; 306:539–53.

    Article  PubMed  CAS  Google Scholar 

  38. Morais AC, Ferreira ST. Folding and stability of a coiled-coil investigated using chemical and physical denaturing agents: Comparative analysis of polymerized and nonpolymerized forms of α-tropomyosin. Int J Biochem Cell Biol 2005; 37:1386–1395.

    Article  PubMed  CAS  Google Scholar 

  39. Nitanai Y, Minakata S, Maeda K et al. Crystal structure of tropomyosin: flexible coiled-coil. Adv Exp Med Biol 2007; 592:137–51.

    Article  PubMed  Google Scholar 

  40. Steinmetz MO, Jelesarov I, Matousek WM et al. Molecular basis of coiled-coil formation. Proc Natl Acad Sci USA 2007; 104:7062–67.

    Article  PubMed  CAS  Google Scholar 

  41. Monteiro PB, Lataro RC, Ferro JA et al. Functional alpha-tropomyosin produced in Escherichia coli. A dipeptide extension can substitute the amino-terminal acetyl group. J Biol Chem 1994; 269:10461–6.

    PubMed  CAS  Google Scholar 

  42. Urbancikova M, Hitchcock-DeGregori SE., Requirement of amino-terminal modification for striated muscle alpha-tropomyosin function. J Biol Chem 1994; 269:24310–5.

    PubMed  CAS  Google Scholar 

  43. Greenfield NJ, Stafford WF, Hitchcock-DeGregori SE. The effect of N-terminal acetylation on the structure of an N-terminal tropomyosin peptide and alpha alpha-tropomyosin. Protein Sci 1994; 3:402–10.

    Article  PubMed  CAS  Google Scholar 

  44. Skoumpla K, Coulton AT, Lehman W et al. Acetylation regulates tropomyosin function in the fission yeast Schizosaccharomyces pombe. J Cell Sci 2007; 120:1635–45.

    Article  PubMed  CAS  Google Scholar 

  45. Polevoda B, Sherman F. Composition and function of the eukaryotic N-terminal acetyltransferase subunits. Biochem Biophys Res Commun 2003; 308:1–11.

    Article  PubMed  CAS  Google Scholar 

  46. Polevoda B, Cardillo TS, Doyle TC et al. Nat3p and Mdm20p are required for function of yeast NatB Nα-terminal acetyltransferase and of actin and tropomyosin. J Biol Chem 2003; 278:30686–97.

    Article  PubMed  CAS  Google Scholar 

  47. Singer JM, Shaw JM. Mdm20 protein functions with Nat3 protein to acetylate Tpm1 protein and regulate tropomyosin-actin interactions in budding yeast. Proc Natl Acad Sci USA 2003; 100:7644–9.

    Article  PubMed  CAS  Google Scholar 

  48. Caesar R, Warringer J, Blomberg A. Physiological importance and identification of novel targets for the N-terminal acetyltransferase NatB. Eucaryotic Cell 2006; 5:268–78.

    Google Scholar 

  49. Kremneva E, Nikolaeva O, Maytum R et al. Thermal unfolding of smooth muscle and nonmuscle tropomyosin α-homodimers with alternatively spliced exons. FEBS J 2006; 273:588–600.

    Article  PubMed  CAS  Google Scholar 

  50. Hitchcock-DeGregori SE, Song Y, Greenfield NJ. Functions of tropomyosin’s periodic repeats. Biochemistry 2002; 41:15036–44.

    Article  PubMed  CAS  Google Scholar 

  51. Greenfield NJ, Swapna GVT, Huang Y et al. The structure of the carboxyl terminus of striated α-tropomyosin in solution reveals an unusual parallel arrangement of interacting α-helices. Biochemistry 2003; 42:614–9.

    Article  PubMed  CAS  Google Scholar 

  52. Greenfield NJ, Palm T, Hitchcock-DeGregori SE Structure and interactions of the carboxyl terminus of striated α-tropomyosin: it is important to be flexible. Biophys J 2002; 83:2754–66.

    Article  PubMed  CAS  Google Scholar 

  53. Wawro B, Greenfield NJ, Wear MA et al. Tropomyosin regulates elongation by form in at the fast-growing end of the actin filament. Biochemistry 2007; 46:8146–55.

    Article  PubMed  CAS  Google Scholar 

  54. McElhinny AS, Kolmerer B, Fowler VM et al. The N-terminal end of nebulin interacts with tropomodulin at the pointed ends of the thin filaments. J Biol Chem 2001; 276:583–92.

    Article  PubMed  CAS  Google Scholar 

  55. Vera C, Sood A, Gao KM et al. Tropomodulin-binding site mapped to residues 7–14 at the N-terminal heptad repeats of tropomyosin isoform 5. Arch Biochem Biophys 2000; 378:16–24.

    Article  PubMed  CAS  Google Scholar 

  56. Vera C, Lao J, Hamelberg D et al. Mapping the tropomyosin isoform 5 binding site on human erythrocyte tropomodulin: Further insights into E-Tmod/TM5 interaction. Arch Biochem Biophys 2005; 444:130–8.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Unit of Actin Cytoskeleton Regulation, Consorzio Mario Negri Sud, Department of Cell Biology and Oncology, Via Nazionale 8a, 6630, Santa Maria Imbaro, Italy

    Mario Gimona

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  1. Mario Gimona
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Editors and Affiliations

  1. Oncology Research Unit, Department of Pharmacology School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia

    Peter Gunning PhD

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Gimona, M. (2008). Dimerization of Tropomyosins. In: Gunning, P. (eds) Tropomyosin. Advances in Experimental Medicine and Biology, vol 644. Springer, New York, NY. https://doi.org/10.1007/978-0-387-85766-4_6

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