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Models of Thin-Filament Regulation

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The Sliding-Filament Theory of Muscle Contraction
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Abstract

While the strength of contraction in our muscles is activated by the frequency of action potentials in its efferent nerves, this chapter is concerned with the way in which calcium ions released by the transverse-tubule system regulate contraction via the thin filament. Each strand of the actin double helix is regulated by overlapping tropomyosin-troponin units, and theories of thin-filament Ca2+-regulation have evolved from seven-site regulation by independent Tm-Tn units switching between two states (the original steric blocking model) or three states (blocked, closed and open), to models with end-to-end Tm interactions. Recent structural studies point to an alternative model in which Tm-Tn protomers join to form a continuous flexible chain (CFC). This chapter presents a quantitative version of the chain model, in which myosin binding in the absence of calcium is blocked by TnI bound to actin. Calcium binding to TnC releases TnI, which allows the chain to make angular Brownian fluctuations about the closed state, from which myosin binding pushes the chain out to a local open state. These models have been tested by solution experiments.

Cooperation is the best form of regulation. anon.

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References

  • Bacchiocchi C, Graceffa P, Lehrer SS (2004) Myosin-induced movement of αα, αβ, and ββ smooth muscle tropomyosin on actin observed by multisite FRET. Biophys J 86:2295–2307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bremel RD, Weber A (1972) Cooperation within actin filament in vertebrate skeletal muscle. Nat New Biol 238:97–101

    Article  CAS  PubMed  Google Scholar 

  • Bremel RD, Murray JM, Weber A (1972) Manifestations of cooperative behaviour in the regulated actin filament during actin-activated ATP hydrolysis in the presence of calcium. Cold Spring Harb Symp Quant Biol 37:267–275

    Article  Google Scholar 

  • Brenner B, Schoenberg M, Chalovich JM, Greene LE, Eisenberg E (1982) Evidence for cross-bridge attachment in relaxed muscle at low ionic strength. Proc Natl Acad Sci USA 79:7288–7291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chalovich JM, Eisenberg E (1982) Inhibition of actomyosin ATPase activity by troponin-tropomyosin without blocking the binding of myosin to actin. J Biol Chem 257:2432–2437

    CAS  PubMed  Google Scholar 

  • Chen Y, Yan B, Chalovich JM, Brenner B (2001) Theoretical kinetic studies of models for binding myosin subfragment-1 to regulated actin: hill model versus Geeves model. Biophys J 80:2338–2349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Doi M, Edwards SF (1988) The theory of polymer dynamics. Oxford University Press, Oxford

    Google Scholar 

  • Dominguez R (2011) Tropomyosin; the gatekeeper’s view of the actin filament revealed. Biophys J 100:797–798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dong W-J, Rosenfeld SS, Wang C-K, Gordon AM, Cheung HC (1996) Kinetic studies of calcium binding to the regulatory site of troponin C from cardiac muscle. J Biol Chem 271:688–694

    Article  CAS  PubMed  Google Scholar 

  • Ebashi S (1963) Third component participating in the superprecipitation of ‘natural actomyosin’. Nature 200:1010

    Article  CAS  PubMed  Google Scholar 

  • Feynman RP, Hibbs AR (1965) Quantum mechanics and path integrals. McGraw Hill, New York/London, reprinted Dover Inc. (2005)

    Google Scholar 

  • Frye J, Klenchin VA, Rayment I (2010) Stucture of the tropomyosin overlap complex from chicken smooth muscle: insight into the diversity of N-terminal recognition. Biochemistry 48:1272–1283

    Google Scholar 

  • Geeves MA (1991) The dynamics of actin and myosin association and the crossbridge model of muscle contraction. Biochem J 274:1–14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Geeves MA (2016) Thin filament regulation. Comprehensive biophys. In: Goldman YE, Ostap EM (eds) Molecular motors and motility, vol 4. Elsevier Press, Amsterdam, pp 251–267

    Google Scholar 

  • Geeves MA, Halsall DJ (1987) Two-step ligand binding and cooperativity: a model to describe the cooperative binding of myosin subfragment 1 to regulated actin. Biophys J 52:215–220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Geeves MA, Lehrer SS (1994) Dynamics of the muscle thin filament regulatory switch: the size of the regulatory unit. Biophys J 67:272–282

    Article  Google Scholar 

  • Geeves MA, Lehrer SS (2002) In: Solaro RJ, Moss RL (eds) Molecular control mechanisms in striated muscle contraction. Kluwer, Dordrecht, pp 247–269

    Chapter  Google Scholar 

  • Geeves MA, Griffiths H, Mijailovich S, Smith D (2011) Cooperative [Ca2+]- dependent regulation of the rate of myosin binding to actin: solution data and the tropomyosin chain model. Biophys J 100:1–9

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Grabarek Z, Grabarek J, Leavis PC, Gergely J (1982) Calcium binding to the Ca2+- specific sites of troponin C in regulated actin and actomyosin. J Biol Chem 258:14098–14102

    Google Scholar 

  • Greenfield NJ, Kotlyanskaya L, Hitchcock-DeGregori S (2009) Structure of the N terminus of a nonmuscle α-tropomyosin in complex with the C terminus: implications for actin binding. Biochemistry 48:1272–1283

    Article  CAS  PubMed  Google Scholar 

  • Haselgrove JC (1972) X-ray evidence for a conformational change in the actin- containing filaments of vertebrate striated muscle. Cold Spring Harb Symp Quant Biol 37:341–352

    Article  Google Scholar 

  • Heeley DH, Belknap B, White HD (2006) Maximal activation of skeletal muscle thin filaments requires both rigor myosin S1 and calcium. J Biol Chem 281:668–676

    Article  CAS  PubMed  Google Scholar 

  • Herzberg O, James MNG (1985) Structure of the calcium regulatory protein troponin- C at 2.8Ã… resolution. Nature 313:653–659

    Article  CAS  PubMed  Google Scholar 

  • Hill AV (1913) The combinations of haemoglobin with oxygen and with carbon monoxide. I. Biochem J 7:471–480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hill TL (1960) Introduction to statistical mechanics. Addison-Wesley, Reading

    Google Scholar 

  • Hill TL, Eisenberg E, Greene LE (1980) Theoretical model for the cooperative equilibrium binding of myosin subfragment 1 to the actin-troponin-tropomyosin complex. Proc Natl Acad Sci USA 77:3186–3190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hitchcock-DeGregori SY, Moraczewska J (2001) Importance of internal regions and the overall length of tropomyosin for actin binding and regulatory function. Biochemistry 40:2104–2112

    Article  CAS  PubMed  Google Scholar 

  • Holmes KC, Lehman W (2008) Gestalt binding of tropomyosin to actin filaments. J Muscle Res Cell Motil 29:213–219

    Article  CAS  PubMed  Google Scholar 

  • Howard J (2001) Mechanics of motor proteins and the cytoskeleton. Sinauer Assoc. Inc., Sunderland

    Google Scholar 

  • Huxley HE (1972) Structural changes in the actin- and myosin-containing filaments during contraction. Cold Spring Harbor Sympos. Quant Biol 37:361–376

    Article  Google Scholar 

  • Johnson JD, Robinson DE, Robertson SP, Schwartz A, Potter JD (1981) In: Grinnell A, Brazier MAB (eds) The regulation of muscle contraction: excitation-contraction coupling. Academic Press, Inc, New York, pp 241–259

    Google Scholar 

  • Lehman W, Hatch V, Korman M, Rosol M, Thomas L, Maytum R, Geeves MA, van Eyk JE, Tobacman LS, Craig R (2000) Tropomyosin and actin isoforms modulate the localization of tropomyosin strands on actin filaments. J Mol Biol 302:593–606

    Article  CAS  PubMed  Google Scholar 

  • Lehman W, Rosol M, Tobacman LS, 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

    Article  CAS  PubMed  Google Scholar 

  • Lehman W, Orzechowksi M, Li XE, Fischer S, Raunser S (2013) Gestalt binding of tropomyosin on actin during thin filament activation. J Muscle Res Cell Motil 34:155–163

    Article  CAS  PubMed  Google Scholar 

  • Lehrer SS, Morris EP (1982) Dual effects of tropomyosin and troponin-tropomyosin on actomyosin subfragment 1 ATPase. J Biol Chem 257:8073–8080

    CAS  PubMed  Google Scholar 

  • Lehrer SS, Golitsina NL, Geeves MA (1997) Actin-tropomyosin activation of myosin subfragment 1 ATPase and thin filament cooperativity. The role of tropomyosin flexibility and end-to-end interaction. Biochemistry 36:13449–13,454

    Article  CAS  PubMed  Google Scholar 

  • Li XE, Holmes KC, Lehman W, Jung HS, Fischer S (2010a) The shape and flexibility of tropomyosin coiled coils: implications for actin filament assembly. J Mol Biol 395:327–339

    Article  CAS  PubMed  Google Scholar 

  • Li XE, Lehman W, Fischer S, Holmes KC (2010b) Curvature variation along the tropomyosin molecule. J Struct Biol 170:307–312

    Article  CAS  PubMed  Google Scholar 

  • Li XE, Lehman W, Fischer S (2010c) The relationship between curvature, flexibility and persistence length in the tropomyosin coiled coil. J Struct Biol 170:313–318

    Article  CAS  PubMed  Google Scholar 

  • Li XE, Tobacman LS, Mun JY, Craig R, Fischer S (2011) Tropomyosin position on F-actin revealed by EM reconstruction and computational chemistry. Biophys J 100:1005–1013

    Article  CAS  PubMed  Google Scholar 

  • Marko JF, Siggia ED (1995) Stretching DNA. Macromolecules 28:8759–8770

    Article  CAS  Google Scholar 

  • Maytum R, Lehrer SS, Geeves MA (1999) Cooperativity and switching within the three-state model of muscle regulation. Biochemistry 38:1102–1110

    Article  CAS  PubMed  Google Scholar 

  • McKay RT, Saltibus LF, Li X, Sykes BD (2000) Energetics of the induced structural change in a Ca2+ regulatory protein: Ca2+ and troponin I peptide binding to the E41A mutant of the N-domain of skeletal troponin C. Biochemistry 39:12731–12738

    Article  CAS  PubMed  Google Scholar 

  • McKillop DFA, Geeves MA (1993) Regulation of the interaction between actin and myosin subfragment 1: evidence for three states of the thin filament. Biophys J 65:693–701

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mijailovich SM, Li X, Griffiths RH, Geeves MA (2012) The Hill model for binding myosin S1 to regulated actin is not equivalent to the McKillop-Geeves model. J Mol Biol 417:112–128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Monod J, Wyman J, Changeux J-P (1965) On the nature of allosteric transitions: a plausible model. J Mol Biol 12:88–118

    Article  CAS  PubMed  Google Scholar 

  • Palm T, Greenfield NJ, Hitchcok-DeGregori SE (2003) Tropomyosin ends determine the stability and functionality of overlap and troponin T complexes. Biophys J 81:3181–3189

    Article  Google Scholar 

  • Palmiter KA, Solaro RJ (1997) Molecular mechanisms regulating the myofilament response to Ca2+: Implications of mutations causal for familial cardiac hypertrophy. Basic Res Cardiology 92:63–74

    Article  CAS  PubMed  Google Scholar 

  • Perry SV (2001) Vertebrate tropomyosin: distribution, properties and function. J Muscle Res Cell Motil 22:5–49

    Article  CAS  PubMed  Google Scholar 

  • Pirani A, Xu C, Hatch V, Craig R, Tobacman LS, Lehman W (2005) Single particle analysis of relaxed and activated muscle thin filaments. J Mol Biol 346:761–772

    Article  CAS  PubMed  Google Scholar 

  • Press WH, Teukolsky SA, Vetterling WT, Flannery BR (1992) Numerical Recipes in Fortran, 2nd edn. Cambridge University Press, Cambridge, pp 729–731

    Google Scholar 

  • Robinson JM, Wang Y, Kerrick GL, Kawai R, Cheung HC (2002) Activation of striated muscle: nearest-neighbour regulatory-unit and cross-bridge influence on myofilament kinetics. J Mol Biol 322:1065–1088

    Article  CAS  PubMed  Google Scholar 

  • Ruegg JC (1988) Calcium in muscle activation. Springer, Berlin

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Smith DA (2001) Path-integral theory of an axially confined worm-like chain. J Phys A Math Gen 34:4507–4523

    Article  Google Scholar 

  • Smith DA, Geeves MA (2003) Cooperative regulation of myosin-actin interactions by a continuous flexible chain II: actin-tropomyosin-troponin and regulation by calcium. Biophys J 84:3168–3180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith DA, Maytum R, Geeves MA (2003) Cooperative regulation of myosin- actin interactions by a continuous flexible chain I: Actin-tropomyosin systems. Biophys J 84:3155–3167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steffen W, Smith D, Sleep J (2003) The working stroke upon myosin-nucleotide complexes binding to actin. Proc Nat Acad Sci USA 100:6434–6439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sundaralingam M, Bergstrom R, Strasburg G, Rao ST, Rowchowdhury P, Greaser M, Wang BC (1985) Molecular structure of troponin C from chicken skeletal muscle at 3. angstrom resolution. Science 227:945–948

    Article  CAS  PubMed  Google Scholar 

  • Takeda S, Yamashita A, Maeda K, Maeda Y (2003) Structure of the core domain of human cardiac troponin in the Ca2+-saturated form. Nature 424:35–41

    Article  CAS  PubMed  Google Scholar 

  • Tobacman LS, Butters CA (2000) A new model of myosin-thin filament binding. J Biol Chem 275:27587–27,593

    CAS  PubMed  Google Scholar 

  • Trybus KM, Taylor EW (1980) Kinetic studies of the cooperative binding of subfragment 1 to regulated actin. Proc Nat Acad Sci USA 77:7209–7213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vassylyev DG, Takeda S, Wakatsuki S, Maeda K, Maeda Y (1998) Crystal structure of troponin C in complex with troponin I fragment at 2.3-Ã… resolution. Proc Nat Acad Sci USA 95:4847–4852

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Wegner A (1980) The interaction of α,α- and α,β-tropomyosin with actin filaments. FEBS Lett 119:245–248

    Article  CAS  PubMed  Google Scholar 

  • Wiggins C, Riveline D, Ott A, Goldstein RE (1998) Trapping and wiggling: elastohydrodynamics of driven microfilaments. Biophys J 74:1043–1060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zou G, Phillips JN Jnr (1994) A cellular automaton model for the regulatory behaviour of muscle thin filaments. Biophys J 67:11–28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Aitchison Smith, D. (2018). Models of Thin-Filament Regulation. In: The Sliding-Filament Theory of Muscle Contraction. Springer, Cham. https://doi.org/10.1007/978-3-030-03526-6_7

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