Skip to main content
SpringerLink
Log in

Tropomyosin and the Steric Mechanism of Muscle Regulation

  • Chapter
Book cover Tropomyosin

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

Abstract

Contraction in all muscles must be precisely regulated and requisite control systems must be able to adjust to changes in physiological and myopathic stimuli. In this chapter, we outline the structural evidence for a steric mechanism that governs muscle activity. The mechanism involves calcium and myosin induced changes in the position of tropomyosin along actin-based thin filaments. This process either blocks or uncovers myosin crossbridge binding sites on actin and consequently regulates crossbridge cycling on thin filaments, the sliding of thin and thick filaments and muscle shortening and force production.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Kabsch W, Mannherz HG, Suck D et al. Atomic structure of actin: DNAase 1 complex. Nature 1990; 347:37–43.

    Article  PubMed  CAS  Google Scholar 

  2. Holmes KC, Kabsch W. Muscle proteins: actin. Current Opinion Struct Biol 1991; 1:270–280.

    Article  CAS  Google Scholar 

  3. Otterbein LR, Graceffa P, Dominguez R. The crystal structure of uncomplexed actin in the ADP state. Science 2001; 293:616–618.

    Article  Google Scholar 

  4. Rould MA, Wan Q, Joel PB et al. Crystal structures of expressed nonpolymerizable monomeric actin in the ADP and ATP states. J Biol Chem 2006; 281:31909–31919.

    Article  PubMed  CAS  Google Scholar 

  5. Rayment I, Rypniewski WR, Schmidt-Bäse K et al. Three-dimensional structure of myosin subfragment-1: A molecular motor. Science 1993a; 261:50–58.

    Article  PubMed  CAS  Google Scholar 

  6. Houdusse A, Sweeney HL. Myosin motors: missing structures and hidden springs. Curr Opin Struct Biol 2001; 11:182–194.

    Article  PubMed  CAS  Google Scholar 

  7. Geeves MA, Holmes KC. The molecular mechanism of muscle contraction. Adv Protein Chem 2005; 71:161–193.

    Article  PubMed  CAS  Google Scholar 

  8. Baghaw CR. Myosin mechanochemistry. Structure 2007; 15:511–512.

    Article  CAS  Google Scholar 

  9. Holmes KC, Popp D, Gebhard W et al. Atomic model of the actin filament. Nature 1990; 347:44–47.

    Article  PubMed  CAS  Google Scholar 

  10. Rayment I, Holden HM, Whittaker M et al. Structure of the actin-myosin complex and its implications for muscle contraction. Science 1993b; 261:58–65.

    Article  PubMed  CAS  Google Scholar 

  11. Holmes KC, Angert I, Kull FJ et al. Electron cryo-microscopy shows how strong binding of myosin to actin releases nucleotide. Nature 2003; 425:423–427.

    Article  PubMed  CAS  Google Scholar 

  12. Cooke R. The sliding filament model: 1972–2004. J Gen Physiol 2004; 123:643–656.

    Article  PubMed  CAS  Google Scholar 

  13. Kull FJ, Endow SA. A new structural state of myosin. Trends Biochem Sci 2004; 29:103–106.

    Article  PubMed  CAS  Google Scholar 

  14. Warshaw DM. Lever arms and necks: a common mechanistic theme across the myosin superfamily. J Muscle Res Cell Motil 2004; 25:467–474.

    Article  PubMed  Google Scholar 

  15. Yang Y, Gourinath S, Kovács M et al. Rigor-like structures from muscle myosins reveal key mechanical elements in the transduction pathways of this allosteric motor. Structure 2007; 15:553–564.

    Article  PubMed  CAS  Google Scholar 

  16. Ebashi S, Endo M. Calcium ion and muscle contraction. Prog Biophys Mol Biol 1968:28, 123–183.

    Article  Google Scholar 

  17. Murray JM, Weber A. Molecular control mechanisms in muscle contraction. Physiol Rev 1973; 53:612–673.

    PubMed  Google Scholar 

  18. Lehman W, Szent-Györgyi AG. Regulation of muscular contraction. Distribution of actin control and myosin control in the animal kingdom. J Gen Physiol 1975; 66:1–30.

    Article  PubMed  CAS  Google Scholar 

  19. Lehman W. Thin-filament-linked regulation in molluscan muscles. Biochim Biophys Acta 1981; 668:349–356.

    PubMed  CAS  Google Scholar 

  20. Greaser M, Gergely J. Reconstitution of troponin activity from three protein components. J Biol Chem 1971; 246:4226–4233.

    PubMed  CAS  Google Scholar 

  21. Hitchcock SE, Huxley HE, Szent-Györgyi AG. Calcium sensitive binding of troponin to actintropomyosin: A two-site model for troponin action. J Mol Biol 1973; 80:825–836.

    Article  PubMed  CAS  Google Scholar 

  22. Potter JD, Gergely J. Troponin, tropomyosin and actin interactions in the Ca2+ regulation of muscle contraction. Biochemistry 1974; 13:2697–2703.

    Article  PubMed  CAS  Google Scholar 

  23. Potter JD, Sheng Z, Pan B-S et al. A direct regulatory role for troponin T and a dual role for troponin C in the Ca2+ regulation of muscle contraction. J Biol Chem 1995; 270:2557–2562.

    Article  PubMed  CAS  Google Scholar 

  24. Tobacman LS. Thin filament-mediated regulation of cardiac contraction. Annu Rev Physiol 1996; 58:447–481.

    Article  PubMed  CAS  Google Scholar 

  25. Takeda S, Yamashita A, Maeda K et al. Structure of the core domain of human cardiac troponin in the Ca2+-saturated form. Nature 2003; 424:35–41.

    Article  PubMed  CAS  Google Scholar 

  26. Vinogradova MV, Stone DB, Malanina GG et al. Ca2+-regulated structural changes in troponin. Proc Natl Acad Sci USA 2005; 102:5038–5043.

    Article  PubMed  CAS  Google Scholar 

  27. Moore PB, Huxley HE, DeRosier DJ. Three-dimensional reconstruction of F-actin, thin filaments and decorated thin filaments. J Mol Biol 1970; 50:279–292.

    Article  PubMed  CAS  Google Scholar 

  28. O’Brien EJ, Bennett PM, Hanson J. Optical diffraction studies of myofibrillar structure. Philos Trans Roy Soc Lond B 1971; 261:201–208.

    Article  CAS  Google Scholar 

  29. Spudich JA, Huxley HE, Finch JT. The regulation of skeletal muscle contraction. II. Structural studies of the interaction of the tropomyosin-troponin complex with actin. J Mol Biol 1972; 72:619–632.

    Article  PubMed  CAS  Google Scholar 

  30. McLachlan AD, Stewart M. The 14-Fold Periodicity in alpha-tropomyosin and the interaction with actin. J Mol Biol 1976; 103:271–298.

    Article  PubMed  CAS  Google Scholar 

  31. Lorenz M, Poole KJV, Popp D et al. An atomic model of the unregulated thin filament obtained by X-ray fiber diffraction on oriented actin-tropomyosin gels. J Mol Biol 1995; 246:108–119.

    Article  PubMed  CAS  Google Scholar 

  32. Hitchcock-DeGregori SE, An Y. Integral repeats and continuous coiled coil are required for binding of striated muscle tropomyosin to the regulated actin filament. J Biol Chem 1996; 271:3600–3603.

    Article  PubMed  CAS  Google Scholar 

  33. Caspar DLD, Cohen C, Longley, W. Tropomyosin: Crystal structure, polymorphism and molecular interactions. J Mol Biol 1969; 41:87–107.

    Article  PubMed  CAS  Google Scholar 

  34. Greenfield NJ, Huang YJ, Swapna GV et al. Solution NMR structure of the junction between tropomyosin molecules: implications for actin binding and regulation. J Mol Biol 2006; 364:80–96.

    Article  PubMed  CAS  Google Scholar 

  35. Ohtsuki I, Masaki T, Nonomura Y et al. Periodic distribution of troponin along the thin filament. J Biochem (Tokyo) 1967; 61:817–819.

    CAS  Google Scholar 

  36. Cohen C, Caspar DLD, Johnson JP et al. Tropomyosin-troponin assembly. Cold Spring Harbor Symp Quant Biol 1972; 37:287–297.

    Google Scholar 

  37. Ohtsuki I. Localization of troponin in thin filaments and in tropomyosin paracrystals. J Biochem (Tokyo) 1974; 75:753–765.

    CAS  Google Scholar 

  38. Flicker PF, Phillips GN, Cohen C. Troponin and its interactions with tropomyosin: An electron microscope study. J Mol Biol 1982; 162:495–501.

    Article  PubMed  CAS  Google Scholar 

  39. Gordon AM, Homsher E, Regnier M. Regulation of contraction in striated muscle. Physiol Rev 2000; 80:853–924.

    PubMed  CAS  Google Scholar 

  40. Regnier M, Rivera AJ, Wang CK et al. Thin filament near-neighbor regulatory unit interactions affect rabbit skeletal muscle steady-state force-Ca2+ relations. J Physiol 2002; 540:485–497.

    Article  PubMed  CAS  Google Scholar 

  41. Wegner A. Equilibrium of the actin-tropomyosin interaction. J Mol Biol 1979; 131:839–853.

    Article  PubMed  CAS  Google Scholar 

  42. Wegner A. The interaction of alpha, alpha-and alpha, beta-tropomyosin with actin filaments. FEBS Lett 1980; 119:245–248.

    Article  PubMed  CAS  Google Scholar 

  43. Wegner A, Walsh TP. Interaction of tropomyosin-troponin with actin filaments. Biochemistry 1981; 20:5633–5642.

    Article  PubMed  CAS  Google Scholar 

  44. Heald RW, Hitchcock-DeGregori SE. The structure of the amino terminus of tropomyosin is critical for binding to actin in the absence and presence of troponin. J Biol Chem 1988; 263:5254–5259.

    PubMed  CAS  Google Scholar 

  45. Hinkle A, Goranson A, Butters CA et al. Roles for the troponin tail domain in thin filament assembly and regulation. A deletional study of cardiac troponin T. J Biol Chem 1999; 274:7157–7164.

    Article  PubMed  CAS  Google Scholar 

  46. 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; 269:10461–10466.

    PubMed  CAS  Google Scholar 

  47. Palm T, Greenfield NJ, Hitchcock-DeGregori SE. Tropomyosin ends determine the stability and functionality of overlap and troponin T complexes. Biophys J 2003; 84:3181–3189.

    Article  PubMed  CAS  Google Scholar 

  48. Huxley HE Structural changes in actin-and myosin-containing filaments during contraction. Cold Spring Harbor Symp Quant Biol 1972; 37:361–376.

    Google Scholar 

  49. Haselgrove JC. X-ray evidence for a conformational change in actin-containing filaments of vertebrate striated muscle. Cold Spring Harbor Symp Quant Biol 1972; 37:341–352.

    Google Scholar 

  50. Parry DAD, Squire JM. Structural role of tropomyosin in muscle regulation: Analysis of the X-ray patterns from relaxed and contracting muscles. J Mol Biol 1973; 75:33–55.

    Article  PubMed  CAS  Google Scholar 

  51. Hanson J, Lowy J. The structure of actin filaments and the origin of the axial periodicity in the I-substance of vertebrate striated muscle. Proc Royal Soc Lond B 1964; 160:449–460.

    Article  CAS  Google Scholar 

  52. Phillips GN, Fillers JP, Cohen C. Tropomyosin crystal structure and muscle regulation. J Mol Biol 1986; 192:111–131.

    Article  PubMed  CAS  Google Scholar 

  53. Al-Khayat HA, Yagi N, Squire JM. Structural changes in actin-tropomyosin during muscle regulation: Computer modelling of low-angle X-ray diffraction data. J Mol Biol 1995; 252:611–632.

    Article  PubMed  CAS  Google Scholar 

  54. Poole KJV, Evans G, Rosenbaum G et al. The effect of crossbridges on the calcium sensitivity of the structural change of the regulated thin filament. Biophys J 1995; 68:A365.

    Google Scholar 

  55. DeRosier DJ, Klug A. Reconstruction of three-dimensional structures from electron micrographs. Nature 1968; 217:130–134.

    Article  Google Scholar 

  56. Squire JM, Morris E. A new look at thin filament regulation in vertebrate skeletal muscle. FASEB J 1998; 12:761–771.

    PubMed  CAS  Google Scholar 

  57. Cohen C, Vibert PJ. Actin filaments: Images and models. In: Squire, JM, Vibert PJ eds. Pibrous Protein Structure. London: Acad. Press, 1987; 283–306.

    Google Scholar 

  58. Squire J. Muscle regulation: a decade of steric blocking. Nature 1981; 291:614–615.

    Article  PubMed  CAS  Google Scholar 

  59. Lehman W, Craig R. The structure of the vertebrate striated muscle thin filament: a tribute to the contributions of Jean Hanson. J. Muscle Research Cell Motility 2004; 25:455–466.

    Article  Google Scholar 

  60. Milligan RA, Whittaker M, Safer D. Molecular structure of F-actin and the location of surface binding sites. Nature 1990; 348:217–221.

    Article  PubMed  CAS  Google Scholar 

  61. Xu C, Craig R, Tobacman L et al. Tropomyosin positions in regulated thin filaments revealed by cryo-electron microscopy. J Mol Biol 1999; 77:985–992.

    CAS  Google Scholar 

  62. Lehman W, Craig R, Vibert P. Ca2+-induced tropomyosin movement in Limulus thin filaments revealed by three dimensional reconstruction. Nature 1994; 368:65–67.

    Article  PubMed  CAS  Google Scholar 

  63. Owen C, Morgan DG, DeRosier DJ. Image analysis of helical objects: The Brandeis helical package. J Struct Biol 1996; 116:167–175.

    Article  PubMed  CAS  Google Scholar 

  64. Lehman W, Vibert P, Uman P et al. Steric-blocking by tropomyosin visualized in relaxed vertebrate muscle thin filaments. J Mol Biol 1995; 251:191–196.

    Article  PubMed  CAS  Google Scholar 

  65. Lehman W, Hatch V, Korman, V et al. Tropomyosin and actin isoforms modulate the localization of tropomyosin strands on actin filaments. J Mol Biol 2000; 302:593–606.

    Article  PubMed  CAS  Google Scholar 

  66. Vibert P, Craig R, Lehman W. Steric-model for activation of muscle thin filaments. J Mol Biol 1997; 266:8–14.

    Article  PubMed  CAS  Google Scholar 

  67. Craig R, Lehman W. Crossbridge and tropomyosin positions observed in native, interacting thick and thin filaments. J Mol Biol 2001; 311:1027–1036.

    Article  PubMed  CAS  Google Scholar 

  68. Pirani A, Xu, C, Hatch V et al. Single particle analysis of relaxed and activated muscle thin filaments. J Mol Biol 2005; 346:761–772.

    Article  PubMed  CAS  Google Scholar 

  69. Pirani A, Vinogradova MV, Curmi PMG et al. An atomic model of the thin filament in the relaxed and Ca2+-activated states. J Mol Biol 2006; 357:707–717.

    Article  PubMed  CAS  Google Scholar 

  70. Poole KJ, Lorenz M, Evans G et al. A comparison of muscle thin filament models obtained from electron microscopy reconstructions and low-angle X-ray fibre diagrams from non-overlap muscle. J Struct Biol 2006; 155:273–284.

    Article  PubMed  CAS  Google Scholar 

  71. Payne MR, Rudnick SE. Regulation of vertebrate striated muscle contraction. Trends Biochem Sci 1989; 14:357–360.

    Article  PubMed  CAS  Google Scholar 

  72. Chalovich JM, Chock PB, Eisenberg E. Mechanism of action of troponin: tropomyosin inhibition of actomyosin ATPase activity without inhibition of myosin binding to actin. J Biol Chem 1981; 256:575–578.

    PubMed  CAS  Google Scholar 

  73. Lehrer SS, Morris EP. Dual Effects of tropomyosin and troponin-tropomyosin on actomyosin subfragment 1 ATPase. J Biol Chem 1982; 257:8073–8080.

    PubMed  CAS  Google Scholar 

  74. McKillop DFA, Geeves MA. Regulation of the interaction between actin and myosin subfragment-1: Evidence for three states of the thin filament. Biophys J 1993; 65:693–701.

    Article  PubMed  CAS  Google Scholar 

  75. Lehrer SS, Geeves MA. The muscle thin filament as a classical cooperative/allosteric regulatory system. J Mol Biol 1998; 277:1081–1089.

    Article  PubMed  CAS  Google Scholar 

  76. Landis CA, Bobkova A, Homsher E et al. The active state of the thin filament is destabilized by an internal deletion in tropomyosin. J Biol Chem 1997; 272:14051–14056.

    Article  PubMed  CAS  Google Scholar 

  77. Rosol M, Lehman W, Landis C et al. Three-dimensional reconstruction of thin filaments containing mutant tropomyosin, Biophys J 2000; 78:918–926.

    Article  Google Scholar 

  78. Kalomoira S, Coulton AT, Lehman W et al. Acetylation regulates tropomyosin function in the fission yeast Schizosaccharomyces pombe. J Cell Sci 2007; 120:1635–1645.

    Article  CAS  Google Scholar 

  79. Maytum R, Konrad M, Hatch, V et al. Ultra short yeast tropomyosins show novel myosin regulation. 2007 (submitted).

    Google Scholar 

  80. Brown JH, Kim KH, Jun G et al. Deciphering the design of the tropomyosin molecule. Proc Natl Acad Sci USA 2001; 98:8496–8501.

    Article  PubMed  CAS  Google Scholar 

  81. Brown JH, Zhou Z, Reshetnikova L et al. Structure of the mid-region of tropomyosin: bending and binding sites for actin. Proc Natl Acad Sci USA 2005; 102:18878–18883.

    Article  PubMed  CAS  Google Scholar 

  82. Chen Y, Lehrer SS. Distances between tropomyosin sites across the muscle thin filament using luminescence resonance energy transfer: evidence for tropomyosin flexibility. Biochemistry 2004; 43:11491–11499.

    Article  PubMed  CAS  Google Scholar 

  83. Singh A, Hitchcock-DeGregori SE. Local destabilization of the tropomyosin coiled coil gives the molecular flexibility required for actin binding. Biochemistry 2003; 42:14114–14121.

    Article  PubMed  CAS  Google Scholar 

  84. Singh A, Hitchcock-DeGregori SE. Dual requirement for flexibility and specificity for binding of the coiled-coil tropomyosin to its target, actin. Structure 2006; 14:43–50.

    Article  PubMed  CAS  Google Scholar 

  85. Brown JH, Cohen C. Regulation of muscle contraction by tropomyosin and troponin: how structure illuminates function. Adv Protein Chem 2005; 71:121–159.

    Article  PubMed  CAS  Google Scholar 

  86. Nitanai Y, Minakata S, Maeda K et al. Crystal structures of tropomyosin: flexible coiled-coil. Adv Exp Med Biol 2007; 592:137–151.

    Article  PubMed  Google Scholar 

  87. Geeves MA, Lehrer SS. Dynamics of the muscle thin filament regulatory switch: the size of the cooperative unit. Biophys J 1994; 67:273–282.

    Article  PubMed  CAS  Google Scholar 

  88. Brandt PW, Diamond MS, Rutchik JS et al. Co-operative interactions between troponin-tropomyosin units extend the length of the thin filament in skeletal muscle. J Mol Biol 1987; 195:885–896.

    Article  PubMed  CAS  Google Scholar 

  89. Phillips GN Jr, Chacko S. Mechanical properties of tropomyosin and implications for muscle regulation. Biopolymers 1996; 38:89–95.

    Article  PubMed  CAS  Google Scholar 

  90. Swenson CA, Stellwagen NC. Flexibility of smooth and skeletal tropomyosins. Biopolymers 1989; 28:955–963.

    Article  PubMed  CAS  Google Scholar 

  91. Wolgemuth CW, Sun SX. Elasticity of alpha-helical coiled coils. Phys Rev Lett 2006; 97:24810.

    Article  CAS  Google Scholar 

  92. Isambert H, Venier P, Maggs AC et al. Flexibility of actin filaments derived from thermal fluctuations. Effect of bound nucleotide, phalloidin and muscle regulatory proteins. J Biol Chem 1995; 270:11437–11444.

    Article  PubMed  CAS  Google Scholar 

  93. Goldmann WH. Binding of tropomyosin-troponin to actin increases filament bending stiffness. Biochem Biophys Res Commun 2000; 276:1225–1228.

    Article  PubMed  CAS  Google Scholar 

  94. Greenberg M, Pant K, Lehman W et al. Mechanical effect of tropomyosin and caldesmon on F-actin. Biophys J 2007 (abstract).

    Google Scholar 

  95. Pant K, Poole KJV, Craig R et al. Structural studies on tropomyosin—F-actin interaction. Biophys J 2007 (abstract).

    Google Scholar 

  96. Bacchiocchi C, Lehrer SS. Ca2+-induced movement of tropomyosin in skeletal muscle thin filaments observed by multi-site FRET. Biophys J 2002; 82:1524–1536.

    Article  PubMed  CAS  Google Scholar 

  97. Bacchiocchi C, Graceffa P, Lehrer SS. Myosin-induced movement of alphaalpha, alphabeta and betabeta smooth muscle tropomyosin on actin observed by multisite FRET. Biophys J 2004; 86:2295–2307.

    Article  PubMed  CAS  Google Scholar 

  98. Holthauzen LM, Correa F, Farah CH. Ca2+-induced rolling of tropomyosin in muscle thin filaments: The alpha-and beta-band hypothesis revisited. J Biol Chem 2004; 279:15204–15213.

    Article  PubMed  CAS  Google Scholar 

  99. Egelman EH. The iterative helical real space reconstruction method: surmounting the problems posed by real polymers. J Struct Biol 2007; 157:83–94.

    Article  PubMed  CAS  Google Scholar 

  100. Egelman EH. A robust algorithm for the reconstruction of helical filaments using single-particle methods. Ultramicroscopy 2000; 85:225–234.

    Article  PubMed  CAS  Google Scholar 

  101. Narita A, Yasunaga T, Ishikawa T et al. Ca2+-induced switching of troponin and tropomyosin on actin filaments as revealed by electron cryo-microscopy. J Mol Biol 2001; 308:241–261.

    Article  PubMed  CAS  Google Scholar 

  102. Sun YB, Brandmeier B, Irving M. Structural changes in troponin in response to Ca2+ and myosin binding to thin filaments during activation of skeletal muscle. Proc Natl Acad Sci 2006; 103:17771–17776.

    Article  PubMed  CAS  Google Scholar 

  103. Lehman W, Rosol M, Tobacman LS et al. Troponin organization on relaxed and activated thin filaments revealed by electron microscopy and three-dimensional reconstruction. J Mol Biol 2001; 307:739–744.

    Article  PubMed  CAS  Google Scholar 

  104. Rarick HM, Tu XH, Solaro RJ et al. The C terminus of cardiac troponin I is essential for full inhibitory activity and Ca2+ sensitivity of rat myofibrils. J Biol Chem 1997; 272:26887–26892.

    Article  PubMed  CAS  Google Scholar 

  105. Kobayashi T, Solaro RJ. Increased Ca2+ affinity of cardiac thin filaments reconstituted with cardiomyopathy-related mutant cardiac troponin. J Biol Chem 2006; 281:13471–13477.

    Article  PubMed  CAS  Google Scholar 

  106. Ramos CH. Mapping subdomains in the C-terminal region of troponin I involved in its binding to troponin C and to thin filament. J Biol Chem 1999; 274:18189–18195.

    Article  PubMed  CAS  Google Scholar 

  107. Foster DB, Noguchi T, VanBuren P et al. C-terminal truncation of cardiac troponin I causes divergent effects on ATPase and force: implications for the pathophysiology of myocardial stunning. Circ Res 2003; 93:917–924.

    Article  PubMed  CAS  Google Scholar 

  108. Luo Y, Leszyk J, Li B et al. Troponin-I interacts with the Met47 region of skeletal muscle actin. Implications for the mechanism of thin filament regulation by calcium. J Mol Biol 2002; 316:429–434.

    Article  PubMed  CAS  Google Scholar 

  109. Leek D, Homsher E, Heller M et al. Unexpected functional effects of TnI inhibitory region replacement with a flexible linker. Biophys J 2007 (abstract).

    Google Scholar 

  110. Hoffman RM, Blumenschein TM, Sykes BD. An interplay between protein disorder and structure confers the Ca2+ regulation of striated muscle. J Mol Biol 2006; 361:625–633.

    Article  PubMed  CAS  Google Scholar 

  111. Galińska-Rakoczy A, Engel P, Tobacman LS et al. Structural basis for the regulation of muscle contraction by troponin and tropomyosin. J Mol Biol 2008; 379(5):929–935.

    Article  PubMed  CAS  Google Scholar 

  112. Patchell VB, Gallon CE, Evans JS et al. The regulatory effects of tropomyosin and troponin-I on the interaction of myosin loop regions with F-actin. J Biol Chem 2005; 280:14469–11475.

    Article  PubMed  CAS  Google Scholar 

  113. Ferguson RE, Sun Y-B, Mercier P et al. In situ orientations of protein domains: Troponin C in skeletal muscle fibers. Mol Cell 2003; 11:865–874.

    Article  PubMed  CAS  Google Scholar 

  114. Lorenz M, Popp D, Holmes KC. Refinement of the F-actin model against X-ray fiber diffraction data by use of a directed mutation algorithm. J Mol Biol 1993; 234: 826–836.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology and Biophysics, Boston University School of Medicine, 715 Albany Street, Boston, MA, 02118, USA

    William Lehman

  2. Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Roger Craig

Authors
  1. William Lehman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roger Craig
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to William Lehman .

Editor information

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

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Landes Bioscience and Springer Science+Business Media

About this chapter

Cite this chapter

Lehman, W., Craig, R. (2008). Tropomyosin and the Steric Mechanism of Muscle Regulation. 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_8

Download citation

Publish with us

Policies and ethics

Search

Navigation