Abstract
The biological production of force and movement can be understood only when it is considered as a molecular phenomenon, as has been recognized for many decades (Huxley, 1957). However, detailed molecular-scale investigations of this process had to await atomic resolution structures of the myosin molecular motor (Rayment et al., 1993). In striated muscles such as skeletal muscle and the heart, the primary regulation of myosin is by the reversible binding of Ca2+ to the thin filament. As was true for understanding myosin’s action, the understanding of myosin’s regulation requires detailed information about the structure of the relevant proteins: the thin filament and its components. These data are now increasingly available, thanks to the determined efforts of many investigators. Albeit incomplete, a molecular appreciation for how movement is controlled is now within reach. This review summarizes recent advances in the structures of actin, tropomyosin, troponin, and the assembled thin filament, focusing on how these results help explain the regulation of cardiac and skeletal muscle contraction, and on some of the questions that remain.
Keywords
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Belmont, L.D., Orlova, A., Drubin, D.G., and Egelman, E.H. (1999). A change in actin conformation associated with filament instability after Pi release. Proc. Natl. Acad. Sci. USA 96, 29–34.
Blumenschein, T.M.A., Tripet, B.P., Hodges, R.S., and Sykes, B.D. (2001). Mapping the interacting regions between troponins T and C: Binding of TnT and TnI peptides to TnC and NMR mapping of the TnT-binding site on TnC. J. Biol. Chem. 276, (In Press).
Bremel, R.D. and Weber, A. (1972). Cooperation within actin filament in vertebrate skeletal muscle. Nature New Biology 238, 97–101.
Brown, J.H., Greenfield, N.J., Dominguez, R., Hitchcock-DeGregori, S.E., and Cohen, C. (2001). Deciphering the design of the tropomyosin molecule. Proc. Natl. Acad. Sci. U. S. A. 98, 8496–8501.
Burhop, J., Rosol, M., Craig, R., Tobacman, L.S., and Lehman, W. (2001). Effects of a cardiomyopathycausing troponin T mutation on thin filament function and structure. J. Biol. Chem. 276, 20788–20794.
Carlier, M.-F. (1991). Actin: protein structure and filament dynamics. J. Biol. Chem. 266, 1–4.
Cassell, M. and Tobacman, L.S. (1996). Opposite effects of myosin subfragment 1 on binding of cardiac troponin and tropomyosin to actin. J. Biol. Chem. 271, 12867–12872.
Chen, X., Cook, R.K., and Rubenstein, P. (1993). Yeast actin with a mutation in the “hydrophobic plug” between subdomains 3 and 4 (L266D) displays a cold-sensitive polymerization defect. J. Cell Biol. 123, 1185–1195.
Eaton, B.L. (1976). Tropomyosin binding to F-actin induced by myosin heads. Science 192, 1337–1339.
Egelman, E.H. and Orlova, A. (1995). New insights into actin filament dynamics. Curr. Opin. Struc. Biol. 5, 172–180.
Feng, L., Kim, E., Lee, W.-L., Miller, C.J., Kuang, B., Reisler, E., and Rubenstein, P. (1997). Fluorescence probing of yeast actin subdomain 3/4 loop 262–274. J. Biol. Chem. 272, 16829–16837.
Flicker, P.F., Phillips, G.N., Jr., and Cohen, C. (1982). Troponin and its interactions with tropomyosin: An electron microscope study. J. Mol. Biol 162, 495–501.
Gagne, S.M., Tsuda, S., Li, M.X., Chandra, M., Smillie, L.B., and Sykes, B.D. (1994). Quantification of the calcium-induced secondary structural changes in the regulatory domain of troponin-C. Protein Science 3, 1961–1974.
Galkin, V.E., Orlova, A., Lukoyanova, N., Wriggers, W., and Egelman, E.H. (2001). Actin depolymerizing factor stabilizes an existing state of F-actin and can change the tilt of F-actin subunits. J. Cell Biol. 153, 75–86.
Gasmi-Seabrook, G.M.C., Howarth, J.W., Finley, N., Abusamhadneh, E., Gaponenko, V., Brito, R.M.M., Solaro, R.J., and Rosevear, P.R. (1999). Solution structures of the C-terminal domain of cardiac troponin C free and bound to the N-terminal domain of cardiac troponin I. Biochemistry 38, 8313–8322.
Geeves, M.A. and Halsall, D.J. (1986). The dynamics of the interaction between myosin subfragment 1 and pyrene-labelled thin filaments, from rabbit skeletal muscle. Proc. R. Soc. Lond. B229, 85–95.
Gordon, A.M., Homsher, E., and Regnier, M. (2000). Regulation of contraction in striated muscle. Physiol. Rev. 80, 853–924.
Greenffield, N.J., Montelione, G.T., Farid, R.S., and Hitchcock-DeGregori, S.E. (1998). The structure of the N-terminus of striated muscle alpha-tropomyosin in a chimeric peptide: nuclear magnetic resonance structure and circular dichroism studies. Biochemistry 37, 7834–7843.
Herzberg, O., Moult, J., and James, M.N.G. (1986). A model for the Ca2+-induced conformational transition of troponin C. A trigger for muscle contraction. J. Biol. Chem. 261, 2638–2644.
Hitchcock, S.E., Huxley, H.E., and Szent-Gyorgyi, A.G. (1973). Calcium sensitive binding of troponin to actin-tropomyosin: A two-site model for troponin action. J. Mol. Biol. 80, 825–836.
Holmes, K.C. (1995). The actomyosin interaction and its control by tropomyosin. Biophys. J. 68, 2s–7s.
Holmes, K.C., Popp, D., Gebhard, W., and Kabsch, W. (1990). Atomic model of the actin filament. Nature 347, 44–49.
Houdusse, A., Love, M.L., Dominguez, R., Grabarek, Z., and Cohen, C. (1997). Structures of four Ca2+-bound troponin C at 2.0 A resolution: further insights into the Ca2+-switch in the calmodulin superfam i ly. Structure 5, 1695–1711.
Huxley, A.F. (1957). Muscle structure and theories of contraction. Prog. Biophys. 7, 255–318.
Isambert, H., Venier, P., Maggs, A.C., Fattoum, A., Kassab, R., Pantaloni, D., and Carlier, M.-F. (1995). Flexibility of actin filaments derived from thermal fluctuations. Effect of bound nucleotide, phalloidin, and muscle regulatory proteins. J. Biol. Chem. 270, 11437–11444.
Kabsch, W., Mannerz, H.G., Suck, D., Pai, E.F., and Holmes, K.C. (1990). Atomic structure of the actin:DNase I complex. Nature 347, 37–44.
Korman, V.L., Hatch, V., Dixon, K., Craig, R., Lehman, W., and Tobacman, L.S. (2000). An actin subdomain 2 mutation that impairs thin filament regulation by troponin and tropomyosin. J. Biol. Chem. 275, 22470–22478.
Kouyama, T. and Mihashi, K. (1981). Fluorimetry study of N-(1-pyrenyl)iodoacetamide labelled F-actin. Local structural change of actin protomer both on polymerization and on binding of heavy meromyosin. Eur. J. Biochem. 114, 33–38.
Landis, C.A., Back, N., Homsher, E., and Tobacman, L.S. (1999). Effects of tropomyosin internal deletions on thin filament function. J. Biol. Chem. 274, 31279–31285.
Landis, C.A., Bobkova, A., Homsher, E., and Tobacman, L.S. (1997). The active state of the thin filament is destabilized by an internal deletion in tropomyosin. J. Biol. Chem. 272, 14051–14056.
Lehman, W., Craig, R., and Vibert, P. (1994). Ca2+-induced tropomyosin movement in Limulus thin filaments revealed by three-dimensional reconstruction. Nature 368, 65–67.
Lehman, W., Hatch, V., Korman, V.L., Rosol, M., Thomas, L.T., Maytum, R., Geeves, M.A., Van Eyk, J.E., Tobacman, L.S., and Craig, R. (2000). Tropomyosin and Actin Isoforms Modulate the Localization of Tropomyosin Strands on Actin Filaments. J. Mol. Biol. 302, 593–606.
Lehman, W., Rosol, M., Tobacman, L.S., and Craig, R. (2001). Troponin Organization on Relaxed and Activated Thin Filaments Revealed by Electron Microscopy and Three-dimensional Reconstruction. J. Mol. Biol 307, 739–744.
Lehman, W., Vibert, P., Uman, P., and Craig, R. (1995). Steric-blocking by Tropomyosin Visualized in Relaxed Vertebrate Muscle Thin filaments. J. Mol. Biol 251, 191–196.
Lehrer, S.S., Golitsina, N.L., and Geeves, M.A. (1997). Actin-tropomyosin activation of myosin subfragment IATPase and thin filament cooperativity. The role of tropomyosin flexibility and endto-end interactions. Biochemistry 36, 13454.
Li, M.X., Spyracopoulos, L., and Sykes, B.D. (1999). Binding of cardiac troponin-I 147–163 induces a structural opening in human cardiac troponin-C. Biochemistry 38, 8298.
Li, Y., Love, M.L., Putkey, J.A., and Cohen, C. (2000). Bepredil opens the regulatory N-terminal domain lobe of cardiac troponin C. Proc. Natl. Acad. Sci., USA 97, 5140–5145.
Lorenz, M., Poole, K.J.V., Popp, D., Rosenbaum, G., and Holmes, K.C. (1995). An atomic model of the unregulated thin filament obtained by x-ray fiber diffraction on oriented actin-tropomyosin gels. J. Mol. Biol. 246, 108–119.
Lorenz, M., Popp, D., and Holmes, K.C. (1993). Refinement of the F-actin model against X-ray fiber diffraction data by the use of a directed mutation algorithm. J. Mol. Biol. 234, 826–836.
Margossian, S.S. and Cohen, C. (1973). Troponin subunit interactions. J. Mol. Biol. 81, 409–413.
Maytum, R., Geeves, M., and Konrad, M. (2001). Actomyosin regulatory properties of yeast tropomyosin are dependent upon N-terminal modification. Biochemistry 39, 11913–11920.
McGough, A., Pope, B., Chiu, W., and Weeds, A. (1997). Cofilin changes the twist of F-actin: implications for actin filament dynamics and cellular function. J. Cell Biol. 138, 771–781.
McLaughlin, P.J., Gooch, J.T., Mannerz, H.-G., and Weeds, A.G. (1993). Structure of gelsolin segment 1-actin complex and the mechanism of filament severing. Nature 364, 685–692.
Mendelson, R.A. and Morris, E.P. (1994). The structure of F-actin. Results of global searches using data from electron microscopy and X-ray crystallography. J. Mol. Biol 240, 138–154.
Milligan, R.A., Whittaker, M., and Safer, D. (1990). Molecular structure of F-actin and location of surface binding sites. Nature 348, 217–221.
Olah, G.A. and Trewhella, J. (1994). A model structure of the muscle protein complex 4Ca2+-troponin C-troponin I derived from small-angle scattering data: implications for regulation. Biochemistry 33, 12800–12806.
Orlova, A., Chen, X., Rubenstein, P.A., and Egelman, E.H. (1997). Modulation of yeast F-actin structure by a mutation in the nucleotide binding cleft. J. Mol. Biol 271, 235–243.
Orlova, A., Prochniewicz, E., and Egelman, E.H. (1995). Structural dynamics of F-actin: II. Cooperativity in structural transitions. J. Mol. Biol. 245, 598–607.
Otterbein, L.R., Graceffa, P., and Dominguez, R. (2001). The crystal structure of uncomplexed actin in the ADP state. Science 293, 708–711.
Page, R., Lindberg, U., and Schutt, C.E. (1998). Domain motions in actin. J. Mol. Biol 280, 463–474.
Potter, J.D. and Gergely, J. (1974). Troponin, tropomyosin, and actin interactions in the Ca2+ regulation of muscle contraction. Biochemistry 13, 2697–2703.
Prochniewicz, E. and Thomas, D.D. (1999). Differences in structural dynamics of muscle and yeast actin accompany differences in functional interactions with myosin. Biochemistry 38, 14860–14867.
Rayment, I., Holden, H.M., Whittaker, M., Yohn, C.B., Lorenz, M., Holmes, K.C., and Milligan, R.A. (1993). Structure of the actin-myosin complex and its implications for muscle contraction. Science 261, 58–65.
Razzaq, A., Schmitz, S., Veigel, C., Molloy, J.E., and Geeves, M.A. (1999). Actin residue Glu93 is identified as an amino acid affecting myosin binding. J. Biol. Chem. 274, 28321–28328.
Rosol, M., Lehman, W., Craig, R., Landis, C., Butters, C., and Tobacman, L.S. (2000). Threedimensional reconstruction of thin filaments containing mutant tropomyosin. Biophys. J. 78, 908–917.
Schutt, C.E., Myslik, J.C., Rozycki, M.D., Goonesekere, N.C.W., and Lindberg, U. (1993). The structure of crystalline profilin:β-actin. Nature 365, 810–816.
Sia, S.K., Li, M.X., Spyracopoulos, L., Gagne, S.M., Liu, W., Putkey, J.A., and Sykes, B.D. (1997). Structure of cardiac muscle troponin C unexpectedly reveals a closed regulatory domain. J. Biol. Chem. 272, 18216–18221.
Stefancsik, R., Jha, P.K., and Sarkar, S. (1998). Identification and mutagenesis of a highly conserved domain in troponin T responsible for troponin I binding: Potential role for coiled coil interaction. Proc. Natl. Acad. Sci. USA 95, 957–962.
Steinmetz, M.O., Stoffler, D., Hoenger, A., Bremer, A., and Aebi, U. (1997). Actin: from cell biology to atomic detail. J. Struct. Biol. 119, 295–320.
Stone, D.B., Timmins, P.A., Schneider, D.K., Krylova, I., Ramos, C.H., Reinach, F.C., and Mendelson, R.A. (1998). The effect of regulatory Ca2+ on the in situ structures of troponin C and troponin I: a neutron scattering study. J. Mol. Biol 281, 689–704.
Strand, J., Nili, M., Homsher, E., and Tobacman, L.S. (2001). Strand, J., Nili, M., Homsher, E. and Tobacman, L.S.: Modulation of Myosin Function by Isoform-Specific Properties of S. Cerevisiae and Muscle Tropomyosins. J. Biol. Chem. 276, (In Press).
Strynadka, N.C., Cherney, M., Sielecki, A.R., Li, M.X., Smillie, L.B., and James, M.N. (1997). Structural details of a calcium-induced molecular switch: X-ray crystallographic analysis of the calciumsaturated N-terminal domain of troponin C at 1.75 A resolution. J. Mol. Biol 273, 238–255.
Swenson, C.A. and Fredrickson, R.S. (1992). Interaction of troponin C and troponin C fragments with troponin I and the troponin I inhibitory peptide. Biochemistry 31, 3420–3429.
Tirion, M.M., ben-Avraham, D., Lorenz, M., and Holmes, K.C. (1995). Normal modes as refinement parameters for the F-actin model. Biophys. J. 68, 5–12.
Tobacman, L.S. (1996). Thin filament-mediated regulation of cardiac contraction. Annu. Rev. Physiol. 58, 447–481.
Tobacman, L.S. and Butters, C.A. (2000). A new model of cooperative myosin-thin filament binding. J. Biol. Chem. 275, 27587–27593.
Tung, C.-S., Wall, M.E., Gallagher, S.C., and Trewhella, J. (2000). A model of troponin-I in complex with troponin-C using hybrid experimental data: The inhibitory region is a β-hairpin. Protein Science 9, 1312–1326.
Van Eyk, J.E., Kay, C.M., and Hodges, R.S. (1991). A comparative study of the interactions of synthetic peptides of the skeletal and cardiac troponin I inhibitory region with skeletal and cardiac troponin C. Biochemistry 30, 9974–9981.
Vassylev, D., Takeda, S., Wakatsuki, S., Maeda, K., and Maeda, Y. (1998). Crystal structure of troponin C in complex with troponin I fragment at 2.3-A resolution. Proc. Natl. Acad. Sci. USA 95, 4847–4852.
Vibert, P., Craig, R., and Lehman, W. (1997). Steric-model for activation of muscle thin filaments. J. Mol. Biol. 266, 8–14.
Williams, D.L. and Greene, L.E. (1983). Comparison of the effects of tropomyosin and troponintropomyosin on the binding of myosin subfragment 1 to actin. Biochemistry 22, 2770–2774.
Xu, C., Craig, R., Tobacman, L.S., Horowitz, R., and Lehman, W. (1999). Tropomyosin postitions in regulated thin filaments revealed by cryoelectron microscopy. Biophys. J. 77, 985–992.
Yarmola, E.G., Sumasundaram, T., Boring, T.A., Spector, I., and Bubb, M.R. (2001). Actin-latrunculin A structure and function. Differential modulation of actin-binding protein function by latrunculin A. J. Biol. Chem. 275, 28120–28127.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2002 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Tobacman, L.S. (2002). Structure and Regulation of Cardiac and Skeletal Muscle Thin Filaments. In: Solaro, R.J., Moss, R.L. (eds) Molecular Control Mechanisms in Striated Muscle Contraction. Advances in Muscle Research, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-015-9926-9_4
Download citation
DOI: https://doi.org/10.1007/978-94-015-9926-9_4
Publisher Name: Springer, Dordrecht
Print ISBN: 978-90-481-6069-3
Online ISBN: 978-94-015-9926-9
eBook Packages: Springer Book Archive