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. 1971 Mar;68(3):685–689. doi: 10.1073/pnas.68.3.685

A Mechanochemical Mechanism for Muscle Contraction

William F Harrington 1,2
PMCID: PMC389017  PMID: 4250777

Abstract

A mechanism for contraction in skeletal muscle is proposed in which the tension-generating site is located within the core of the thick (myosin) filament, specifically within the trypsin-sensitive hinge region of the myosin rod. The force-developing mechanism is thought to be the transfer of energy from ATP splitting in the globular head of one molecule directly to the hinge region of an adjoining molecule, resulting in a phase transition from crystalline to amorphous within the hinge segment of the second molecule. Binding of MgATP at the actinmyosin interface is considered to be a release mechanism. The model leads to out-of-phase oscillating movement of the cross bridges.

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Selected References

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

  1. EBASHI S. Calcium binding activity of vesicular relaxing factor. J Chir (Paris) 1961 Sep;82:236–244. doi: 10.1093/oxfordjournals.jbchem.a127439. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. Eisenberg E., Moos C. The adenosine triphosphatase activity of acto-heavy meromyosin. A kinetic analysis of actin activation. Biochemistry. 1968 Apr;7(4):1486–1489. doi: 10.1021/bi00844a035. [DOI] [PubMed] [Google Scholar]
  5. Finlayson B., Lymn R. W., Taylor E. W. Studies on the kinetics of formation and dissociation of the actomyosin complex. Biochemistry. 1969 Mar;8(3):811–819. doi: 10.1021/bi00831a008. [DOI] [PubMed] [Google Scholar]
  6. Finlayson B., Taylor E. W. Hydrolysis of nucleoside triphosphates by myosin during the transient state. Biochemistry. 1969 Mar;8(3):802–810. doi: 10.1021/bi00831a007. [DOI] [PubMed] [Google Scholar]
  7. Flory P. J. Role of Crystallization in Polymers and Proteins. Science. 1956 Jul 13;124(3211):53–60. doi: 10.1126/science.124.3211.53. [DOI] [PubMed] [Google Scholar]
  8. Fuchs F., Briggs F. N. The site of calcium binding in relation to the activation of myofibrillar contraction. J Gen Physiol. 1968 May;51(5):655–676. doi: 10.1085/jgp.51.5.655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gershman L. C., Dreizen P., Stracher A. Subunit structure of myosin, II. Heavy and light alkali components. Proc Natl Acad Sci U S A. 1966 Sep;56(3):966–973. doi: 10.1073/pnas.56.3.966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Godfrey J. E., Harrington W. F. Self-association in the myosin system at high ionic strength. II. Evidence for the presence of a monomer--dimer equilibrium. Biochemistry. 1970 Feb 17;9(4):894–908. doi: 10.1021/bi00806a026. [DOI] [PubMed] [Google Scholar]
  11. HOEVE C. A., WILLIS Y. A. Elasticity of the fibrous muscle proteins. Biochemistry. 1963 Mar-Apr;2:279–282. doi: 10.1021/bi00902a013. [DOI] [PubMed] [Google Scholar]
  12. Huxley H. E., Brown W. The low-angle x-ray diagram of vertebrate striated muscle and its behaviour during contraction and rigor. J Mol Biol. 1967 Dec 14;30(2):383–434. doi: 10.1016/s0022-2836(67)80046-9. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. KIELLEY W. W., HARRINGTON W. F. A model for the myosin molecule. Biochim Biophys Acta. 1960 Jul 15;41:401–421. doi: 10.1016/0006-3002(60)90037-8. [DOI] [PubMed] [Google Scholar]
  15. Lowey S., Slayter H. S., Weeds A. G., Baker H. Substructure of the myosin molecule. I. Subfragments of myosin by enzymic degradation. J Mol Biol. 1969 May 28;42(1):1–29. doi: 10.1016/0022-2836(69)90483-5. [DOI] [PubMed] [Google Scholar]
  16. Lymn R. W., Taylor E. W. Transient state phosphate production in the hydrolysis of nucleoside triphosphates by myosin. Biochemistry. 1970 Jul 21;9(15):2975–2983. doi: 10.1021/bi00817a007. [DOI] [PubMed] [Google Scholar]
  17. MUELLER H., PERRY S. V. The degradation of heavy meromyosin by trypsin. Biochem J. 1962 Dec;85:431–439. doi: 10.1042/bj0850431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mandelkern L., Posner A. S., Diorio A. F., Laki K. MECHANISM OF CONTRACTION IN THE MUSCLE FIBER-ATP SYSTEM. Proc Natl Acad Sci U S A. 1959 Jun;45(6):814–819. doi: 10.1073/pnas.45.6.814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Miller A., Tregear R. T. Evidence concerning crossbridge attachment during muscle contraction. Nature. 1970 Jun 13;226(5250):1060–1061. doi: 10.1038/2261060a0. [DOI] [PubMed] [Google Scholar]
  20. Morales M. F. Conformation and displacement in muscle contraction. Proc Natl Acad Sci U S A. 1970 Oct;67(2):572–578. doi: 10.1073/pnas.67.2.572. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pepe F. A. The myosin filament. I. Structural organization from antibody staining observed in electron microscopy. J Mol Biol. 1967 Jul 28;27(2):203–225. doi: 10.1016/0022-2836(67)90016-2. [DOI] [PubMed] [Google Scholar]
  22. SCHWARZ G. ON THE KINETICS OF THE HELIX-COIL TRANSITION OF POLYPEPTIDES IN SOLUTION. J Mol Biol. 1965 Jan;11:64–77. doi: 10.1016/s0022-2836(65)80171-1. [DOI] [PubMed] [Google Scholar]
  23. Segal D. M., Harrington W. F. The tritium-hydrogen exchange of myosin and its proteolytic fragments. Biochemistry. 1967 Mar;6(3):768–787. doi: 10.1021/bi00855a018. [DOI] [PubMed] [Google Scholar]
  24. Segal D. M., Himmelfarb S., Harrington W. F. Composition and mass of peptides released during tryptic and chymotryptic hydrolysis of myosin. J Biol Chem. 1967 Mar 25;242(6):1241–1252. [PubMed] [Google Scholar]
  25. Slayter H. S., Lowey S. Substructure of the myosin molecule as visualized by electron microscopy. Proc Natl Acad Sci U S A. 1967 Oct;58(4):1611–1618. doi: 10.1073/pnas.58.4.1611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Taylor E. W., Lymn R. W., Moll G. Myosin-product complex and its effect on the steady-state rate of nucleoside triphosphate hydrolysis. Biochemistry. 1970 Jul 21;9(15):2984–2991. doi: 10.1021/bi00817a008. [DOI] [PubMed] [Google Scholar]
  27. WEBER A., HERZ R., REISS I. On the mechanism of the relaxing effect of fragmented sarcoplasmic reticulum. J Gen Physiol. 1963 Mar;46:679–702. doi: 10.1085/jgp.46.4.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. WEBER A., HERZ R., REISS I. THE REGULATION OF MYOFIBRILLAR ACTIVITY BY CALCIUM. Proc R Soc Lond B Biol Sci. 1964 Oct 27;160:489–501. doi: 10.1098/rspb.1964.0063. [DOI] [PubMed] [Google Scholar]
  29. WEBER A., WINICUR S. The role of calcium in the superprecipitation of actomyosin. J Biol Chem. 1961 Dec;236:3198–3202. [PubMed] [Google Scholar]
  30. WOODS E. F., HIMMELFARB S., HARRINGTON W. F. Studies on the structure of myosin in solution. J Biol Chem. 1963 Jul;238:2374–2385. [PubMed] [Google Scholar]
  31. YOUNG D. M., HIMMELFARB S., HARRINGTON W. F. ON THE STRUCTURAL ASSEMBLY OF THE POLYPEPTIDE CHAINS OF HEAVY MEROMYOSIN. J Biol Chem. 1965 Jun;240:2428–2436. [PubMed] [Google Scholar]

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