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. 1975 Jul;15(7):707–723. doi: 10.1016/S0006-3495(75)85849-8

Calcium regulation of muscle contraction.

A G Szent-Györgyi
PMCID: PMC1334730  PMID: 806311

Abstract

Calcium triggers contraction by reaction with regulatory proteins that in the absence of calcium prevent interaction of actin and myosin. Two different regulatory systems are found in different muscles. In actin-linked regulation troponin and tropomyosin regulate actin by blocking sites on actin required for complex formation with myosin; in myosin-linked regulation sites on myosin are blocked in the absence of calcium. The major features of actin control are as follows: there is a requirement for tropomyosin and for a troponin complex having three different subunits with different functions; the actin displays a cooperative behavior; and a movement of tropomyosin occurs controlled by the calcium binding on troponin. Myosin regulation is controlled by a regulatory subunit that can be dissociated in scallop myosin reversibly by removing divalent cations with EDTA. Myosin control can function with pure actin in the absence of tropomyosin. Calcium binding and regulation of molluscan myosins depend on the presence of regulatory light chains. It is proposed that the light chains function by sterically blocking myosin sites in the absence of calcium, and that the "off" state of myosin requires cooperation between the two myosin heads. Both myosin control and actin control are widely distributed in different organisms. Many invertebrates have muscles with both types of regulation. Actin control is absent in the muscles of molluscs and in several minor phyla that lack troponin. Myosin control is not found in striated vertebrate muscles and in the fast muscles of crustacean decapods, although regulatory light chains are present. While in vivo myosin control may not be excluded from vertebrate striated muscles, myosin control may be absent as a result of mutations of the myosin heavy chain.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bullard B., Dabrowska R., Winkelman L. The contractile and regulatory proteins of insect flight muscle. Biochem J. 1973 Oct;135(2):277–286. doi: 10.1042/bj1350277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Caspar D. L., Cohen C., Longley W. Tropomyosin: crystal structure, polymorphism and molecular interactions. J Mol Biol. 1969 Apr 14;41(1):87–107. doi: 10.1016/0022-2836(69)90128-4. [DOI] [PubMed] [Google Scholar]
  3. Collins J. H. Homology of myosin light chains, troponin-C and parvalbumins deduced from comparison of their amino acid sequences. Biochem Biophys Res Commun. 1974 May 7;58(1):301–308. doi: 10.1016/0006-291x(74)90927-9. [DOI] [PubMed] [Google Scholar]
  4. Collins J. H., Potter J. D., Horn M. J., Wilshire G., Jackman N. The amino acid sequence of rabbit skeletal muscle troponin C: gene replication and homology with calcium-binding proteins from carp and hake muscle. FEBS Lett. 1973 Nov 1;36(3):268–272. doi: 10.1016/0014-5793(73)80388-6. [DOI] [PubMed] [Google Scholar]
  5. EBASHI S. THIRD COMPONENT PARTICIPATING IN THE SUPERPRECIPITATION OF 'NATURAL ACTOMYOSIN'. Nature. 1963 Dec 7;200:1010–1010. doi: 10.1038/2001010a0. [DOI] [PubMed] [Google Scholar]
  6. Ebashi S., Endo M. Calcium ion and muscle contraction. Prog Biophys Mol Biol. 1968;18:123–183. doi: 10.1016/0079-6107(68)90023-0. [DOI] [PubMed] [Google Scholar]
  7. Ebashi S., Endo M., Otsuki I. Control of muscle contraction. Q Rev Biophys. 1969 Nov;2(4):351–384. doi: 10.1017/s0033583500001190. [DOI] [PubMed] [Google Scholar]
  8. Ebashi S., Kodama A. A new protein factor promoting aggregation of tropomyosin. J Biochem. 1965 Jul;58(1):107–108. doi: 10.1093/oxfordjournals.jbchem.a128157. [DOI] [PubMed] [Google Scholar]
  9. Eisenberg E., Kielley W. W. Native tropomyosin: effect on the interaction of actin with heavy meromyosin and subfragment-1. Biochem Biophys Res Commun. 1970 Jul 13;40(1):50–56. doi: 10.1016/0006-291x(70)91044-2. [DOI] [PubMed] [Google Scholar]
  10. Elzinga M., Collins J. H., Kuehl W. M., Adelstein R. S. Complete amino-acid sequence of actin of rabbit skeletal muscle. Proc Natl Acad Sci U S A. 1973 Sep;70(9):2687–2691. doi: 10.1073/pnas.70.9.2687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Greaser M. L., Gergely J. Reconstitution of troponin activity from three protein components. J Biol Chem. 1971 Jul 10;246(13):4226–4233. [PubMed] [Google Scholar]
  12. HASSELBACH W., MAKINOSE M. [The calcium pump of the "relaxing granules" of muscle and its dependence on ATP-splitting]. Biochem Z. 1961;333:518–528. [PubMed] [Google Scholar]
  13. Hartshorne D. J., Mueller H. Fractionation of troponin into two distinct proteins. Biochem Biophys Res Commun. 1968 Jun 10;31(5):647–653. doi: 10.1016/0006-291x(68)90610-4. [DOI] [PubMed] [Google Scholar]
  14. Hartshorne D. J., Pyun H. Y. Calcium binding by the troponin complex, and the purification and properties of troponin A. Biochim Biophys Acta. 1971 Mar 23;229(3):698–711. doi: 10.1016/0005-2795(71)90286-8. [DOI] [PubMed] [Google Scholar]
  15. Haselgrove J. C. X-ray evidence for conformational changes in the myosin filaments of vertebrate striated muscle. J Mol Biol. 1975 Feb 15;92(1):113–143. doi: 10.1016/0022-2836(75)90094-7. [DOI] [PubMed] [Google Scholar]
  16. Head J. F., Perry S. V. The interaction of the calcium-binding protein (troponin C) with bivalent cations and the inhibitory protein (troponin I). Biochem J. 1974 Feb;137(2):145–154. doi: 10.1042/bj1370145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hitchcock S. E., Huxley H. E., Szent-Györgyi A. G. Calcium sensitive binding of troponin to actin-tropomyosin: a two-site model for troponin action. J Mol Biol. 1973 Nov 15;80(4):825–836. doi: 10.1016/0022-2836(73)90212-x. [DOI] [PubMed] [Google Scholar]
  18. Hitchcock S. E. Regulation of muscle contraction: bindings of troponin and its components to actin and tropomyosin. Eur J Biochem. 1975 Mar 17;52(2):255–263. doi: 10.1111/j.1432-1033.1975.tb03993.x. [DOI] [PubMed] [Google Scholar]
  19. Huxley H. E. The mechanism of muscular contraction. Science. 1969 Jun 20;164(3886):1356–1365. doi: 10.1126/science.164.3886.1356. [DOI] [PubMed] [Google Scholar]
  20. Jahromi S. S., Atwood H. L. Structural and contractile properties of lobster leg-muscle fibers. J Exp Zool. 1971 Apr;176(4):475–486. doi: 10.1002/jez.1401760409. [DOI] [PubMed] [Google Scholar]
  21. Kendrick-Jones J., Lehman W., Szent-Györgyi A. G. Regulation in molluscan muscles. J Mol Biol. 1970 Dec 14;54(2):313–326. doi: 10.1016/0022-2836(70)90432-8. [DOI] [PubMed] [Google Scholar]
  22. Lehman W., Bullard B., Hammond K. Calcium-dependent myosin from insect flight muscles. J Gen Physiol. 1974 May;63(5):553–563. doi: 10.1085/jgp.63.5.553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Margossian S. S., Cohen C. Letter: Troponin subunit interactions. J Mol Biol. 1973 Dec 15;81(3):409–413. doi: 10.1016/0022-2836(73)90150-2. [DOI] [PubMed] [Google Scholar]
  24. Mercola D., Bullard B., Priest J. Crystallisation of tropinin-C. Nature. 1975 Apr 17;254(5501):634–635. doi: 10.1038/254634a0. [DOI] [PubMed] [Google Scholar]
  25. Moore P. B., Huxley H. E., DeRosier D. J. Three-dimensional reconstruction of F-actin, thin filaments and decorated thin filaments. J Mol Biol. 1970 Jun 14;50(2):279–295. doi: 10.1016/0022-2836(70)90192-0. [DOI] [PubMed] [Google Scholar]
  26. Morimoto K., Harrington W. F. Substructure of the thick filament of vertebrate striated muscle. J Mol Biol. 1974 Feb 15;83(1):83–97. doi: 10.1016/0022-2836(74)90425-2. [DOI] [PubMed] [Google Scholar]
  27. Murray A. C., Kay C. M. Hydrodynamic and optical properties of troponin A. Demonstration of a conformational change upon binding calcium ion. Biochemistry. 1972 Jul 4;11(14):2622–2627. doi: 10.1021/bi00764a012. [DOI] [PubMed] [Google Scholar]
  28. Nachmias V., Asch A. Actin mediated calcium dependency of actomyosin in a myxomycete. Biochem Biophys Res Commun. 1974 Sep 23;60(2):656–664. doi: 10.1016/0006-291x(74)90291-5. [DOI] [PubMed] [Google Scholar]
  29. O'Brien E. J., Bennett P. M., Hanson J. Optical diffraction studies of myofibrillar structure. Philos Trans R Soc Lond B Biol Sci. 1971 May 27;261(837):201–208. doi: 10.1098/rstb.1971.0051. [DOI] [PubMed] [Google Scholar]
  30. Otsuki I. Localization of troponin in thin filament and tropomyosin paracrystal. J Biochem. 1974 Apr;75(4):753–765. doi: 10.1093/oxfordjournals.jbchem.a130448. [DOI] [PubMed] [Google Scholar]
  31. Otsuki I., Masaki T., Nonomura Y., Ebashi S. Periodic distribution of troponin along the thin filament. J Biochem. 1967 Jun;61(6):817–819. doi: 10.1093/oxfordjournals.jbchem.a128619. [DOI] [PubMed] [Google Scholar]
  32. Parry D. A., Squire J. M. Structural role of tropomyosin in muscle regulation: analysis of the x-ray diffraction patterns from relaxed and contracting muscles. J Mol Biol. 1973 Mar 25;75(1):33–55. doi: 10.1016/0022-2836(73)90527-5. [DOI] [PubMed] [Google Scholar]
  33. Potter J. D., Gergely J. Troponin, tropomyosin, and actin interactions in the Ca2+ regulation of muscle contraction. Biochemistry. 1974 Jun 18;13(13):2697–2703. doi: 10.1021/bi00710a007. [DOI] [PubMed] [Google Scholar]
  34. Regenstein J. M., Szent-Gyäorgyi A. G. Regulatory proteins of lobster striated muscle. Biochemistry. 1975 Mar 11;14(5):917–925. doi: 10.1021/bi00676a007. [DOI] [PubMed] [Google Scholar]
  35. Spudich J. A., Huxley H. E., Finch J. T. Regulation of skeletal muscle contraction. II. Structural studies of the interaction of the tropomyosin-troponin complex with actin. J Mol Biol. 1972 Dec 30;72(3):619–632. doi: 10.1016/0022-2836(72)90180-5. [DOI] [PubMed] [Google Scholar]
  36. Szent-Györgyi A. G., Cohen C., Kendrick-Jones J. Paramyosin and the filaments of molluscan "catch" muscles. II. Native filaments: isolation and characterization. J Mol Biol. 1971 Mar 14;56(2):239–258. doi: 10.1016/0022-2836(71)90462-1. [DOI] [PubMed] [Google Scholar]
  37. Szent-Györgyi A. G., Szentkiralyi E. M., Kendrick-Jonas J. The light chains of scallop myosin as regulatory subunits. J Mol Biol. 1973 Feb 25;74(2):179–203. doi: 10.1016/0022-2836(73)90106-x. [DOI] [PubMed] [Google Scholar]
  38. Tufty R. M., Kretsinger R. H. Troponin and parvalbumin calcium binding regions predicted in myosin light chain and T4 lysozyme. Science. 1975 Jan 17;187(4172):167–169. doi: 10.1126/science.1111094. [DOI] [PubMed] [Google Scholar]
  39. Van Eerd J. P., Kawasaki Y. Effect of calcium(II) on the interaction between the subunits of troponin and tropomyosin. Biochemistry. 1973 Nov 20;12(24):4972–4980. doi: 10.1021/bi00748a024. [DOI] [PubMed] [Google Scholar]
  40. Vibert P. J., Haselgrove J. C., Lowy J., Poulsen F. R. Structural changes in actin-containing filaments of muscle. J Mol Biol. 1972 Nov 28;71(3):757–767. doi: 10.1016/s0022-2836(72)80036-6. [DOI] [PubMed] [Google Scholar]
  41. Weber A., Murray J. M. Molecular control mechanisms in muscle contraction. Physiol Rev. 1973 Jul;53(3):612–673. doi: 10.1152/physrev.1973.53.3.612. [DOI] [PubMed] [Google Scholar]
  42. Weeds A. G., McLachlan A. D. Structural homology of myosin alkali light chains, troponin C and carp calcium binding protein. Nature. 1974 Dec 20;252(5485):646–649. doi: 10.1038/252646a0. [DOI] [PubMed] [Google Scholar]

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