Skip to main content
NCBI home page
Biophysical Journal logoLink to Biophysical Journal
. 1987 Feb;51(2):227–243. doi: 10.1016/S0006-3495(87)83328-3

Possible role of helix-coil transitions in the microscopic mechanism of muscle contraction.

J Skolnick
PMCID: PMC1329883  PMID: 3828457

Abstract

Local helix-coil transitions in the coiled coil portion of myosin have long been implicated as a possible origin of tension generation in muscle. From a statistical mechanical theory of conformational transitions in coiled coils, the free energy required to form a randomly coiled bubble in the hinge region of myosin of the type conjectured by Harrington (Harrington, W. F., 1979, Proc. Natl. Acad. Sci. USA, 76:5066-5070) is estimated to be approximately 25 kcal/mol. Unfortunately this is far more than the free energy available from ATP hydrolysis if the crossbridges operate independently. Thus, in solution such bubbles are predicted to be absent, and the theory requires that the rod portion of myosin be a hingeless, continuously deforming rod. While such bubble formation in vivo cannot be entirely ruled out, it appears to be unlikely. We further conjecture that in solution the swivel located between myosin subfragments 1 and 2 (S-2 and S-1) is due to a locally random conformation of the chains caused by the presence of a proline residue at the point that physically separates the coiled coil from the globular portion of myosin. On attachment of S-1 to actin in the strong binding state, the configurational entropy of the random coil in the swivel region is greatly reduced relative to the case where the ends are free. This produces a spontaneous coil-to-helix transition in the swivel region that causes rotation of S-1 and the translation of actin. Thus, the model predicts that the actin filaments are pushed rather than pulled past the thick filaments by the crossbridges. The specific mechanism of force generation is examined in detail, and a simple statistical mechanical realization of the model is proposed. We find that the model gives a substantial number of qualitative and at times quantitative predictions in accord with experiment, and is particularly appealing in that it provides a simple means of free energy transduction--the well known fact that topological constraints shift the equilibrium between helical and random coil states.

Full text

PDF
227

Selected References

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

  1. Barden J. A., Mason P. Muscle crossbridge stroke and activity revealed by optical diffraction. Science. 1978 Mar 17;199(4334):1212–1213. doi: 10.1126/science.415364. [DOI] [PubMed] [Google Scholar]
  2. Bernengo J. C., Cardinaud R. State of myosin in solution. Electric birefringence and dynamic light-scattering studies. J Mol Biol. 1982 Aug 15;159(3):501–517. doi: 10.1016/0022-2836(82)90298-4. [DOI] [PubMed] [Google Scholar]
  3. Borejdo J., Putnam S., Morales M. F. Fluctuations in polarized fluorescence: evidence that muscle cross bridges rotate repetitively during contraction. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6346–6350. doi: 10.1073/pnas.76.12.6346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cardinaud R., Bernengo J. C. Electric birefringence study of rabbit skeletal myosin subfragments HMM, LMM, and rod in solution. Biophys J. 1985 Nov;48(5):751–763. doi: 10.1016/S0006-3495(85)83833-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cooke R., Franks K. E. Generation of force by single-headed myosin. J Mol Biol. 1978 Apr 15;120(3):361–373. doi: 10.1016/0022-2836(78)90424-2. [DOI] [PubMed] [Google Scholar]
  6. Craig R., Trinick J., Knight P. Discrepancies in length of myosin head. Nature. 1986 Apr 24;320(6064):688–688. doi: 10.1038/320688b0. [DOI] [PubMed] [Google Scholar]
  7. Dos Remedios C. G., Millikan R. G., Morales M. F. Polarization of tryptophan fluorescence from single striated muscle fibers. A molecular probe of contractile state. J Gen Physiol. 1972 Jan;59(1):103–120. doi: 10.1085/jgp.59.1.103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Eads T. M., Mandelkern L. Backbone and side-chain motion in myosin, subfragment 1, and rod determined by natural abundance carbon-13 NMR. J Biol Chem. 1984 Sep 10;259(17):10689–10694. [PubMed] [Google Scholar]
  9. Eisenberg E., Greene L. E. The relation of muscle biochemistry to muscle physiology. Annu Rev Physiol. 1980;42:293–309. doi: 10.1146/annurev.ph.42.030180.001453. [DOI] [PubMed] [Google Scholar]
  10. Eisenberg E., Hill T. L. Muscle contraction and free energy transduction in biological systems. Science. 1985 Mar 1;227(4690):999–1006. doi: 10.1126/science.3156404. [DOI] [PubMed] [Google Scholar]
  11. Eisenberg E., Zobel C. R., Moos C. Subfragment 1 of myosin: adenosine triphophatase activation by actin. Biochemistry. 1968 Sep;7(9):3186–3194. doi: 10.1021/bi00849a022. [DOI] [PubMed] [Google Scholar]
  12. Elliott A., Offer G. Shape and flexibility of the myosin molecule. J Mol Biol. 1978 Aug 25;123(4):505–519. doi: 10.1016/0022-2836(78)90204-8. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Ford L. E., Huxley A. F., Simmons R. M. Tension responses to sudden length change in stimulated frog muscle fibres near slack length. J Physiol. 1977 Jul;269(2):441–515. doi: 10.1113/jphysiol.1977.sp011911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Goody R. S., Holmes K. C. Cross-bridges and the mechanism of muscle contraction. Biochim Biophys Acta. 1983 Apr 15;726(1):13–39. doi: 10.1016/0304-4173(83)90009-5. [DOI] [PubMed] [Google Scholar]
  16. Gordon A. M., Huxley A. F., Julian F. J. The variation in isometric tension with sarcomere length in vertebrate muscle fibres. J Physiol. 1966 May;184(1):170–192. doi: 10.1113/jphysiol.1966.sp007909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. HUXLEY A. F. Muscle structure and theories of contraction. Prog Biophys Biophys Chem. 1957;7:255–318. [PubMed] [Google Scholar]
  18. HUXLEY H. E. The double array of filaments in cross-striated muscle. J Biophys Biochem Cytol. 1957 Sep 25;3(5):631–648. doi: 10.1083/jcb.3.5.631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Harrington W. F. A mechanochemical mechanism for muscle contraction. Proc Natl Acad Sci U S A. 1971 Mar;68(3):685–689. doi: 10.1073/pnas.68.3.685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Harrington W. F. On the origin of the contractile force in skeletal muscle. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5066–5070. doi: 10.1073/pnas.76.10.5066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Heuser J. E., Cooke R. Actin-myosin interactions visualized by the quick-freeze, deep-etch replica technique. J Mol Biol. 1983 Sep 5;169(1):97–122. doi: 10.1016/s0022-2836(83)80177-6. [DOI] [PubMed] [Google Scholar]
  22. Highsmith S., Akasaka K., Konrad M., Goody R., Holmes K., Wade-Jardetzky N., Jardetzky O. Internal motions in myosin. Biochemistry. 1979 Sep 18;18(19):4238–4244. doi: 10.1021/bi00586a031. [DOI] [PubMed] [Google Scholar]
  23. Highsmith S., Cooke R. Evidence for actomyosin conformational changes involved in tension generation. Cell Muscle Motil. 1983;4:207–237. [PubMed] [Google Scholar]
  24. Highsmith S., Eden D. Myosin subfragment 1 has tertiary structural domains. Biochemistry. 1986 Apr 22;25(8):2237–2242. doi: 10.1021/bi00356a058. [DOI] [PubMed] [Google Scholar]
  25. Highsmith S., Kretzschmar K. M., O'Konski C. T., Morales M. F. Flexibility of myosin rod, light meromyosin, and myosin subfragment-2 in solution. Proc Natl Acad Sci U S A. 1977 Nov;74(11):4986–4990. doi: 10.1073/pnas.74.11.4986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Huxley A. F., Simmons R. M. Proposed mechanism of force generation in striated muscle. Nature. 1971 Oct 22;233(5321):533–538. doi: 10.1038/233533a0. [DOI] [PubMed] [Google Scholar]
  27. Huxley H. E., Simmons R. M., Faruqi A. R., Kress M., Bordas J., Koch M. H. Millisecond time-resolved changes in x-ray reflections from contracting muscle during rapid mechanical transients, recorded using synchrotron radiation. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2297–2301. doi: 10.1073/pnas.78.4.2297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. Huxley H. E. The structural basis of muscular contraction. Proc R Soc Lond B Biol Sci. 1971 Jun 29;178(1051):131–149. doi: 10.1098/rspb.1971.0057. [DOI] [PubMed] [Google Scholar]
  30. Hvidt S., Chang T., Yu H. Rigidity of myosin and myosin rod by electric birefringence. Biopolymers. 1984 Jul;23(7):1283–1294. doi: 10.1002/bip.360230712. [DOI] [PubMed] [Google Scholar]
  31. Hvidt S., Nestler F. H., Greaser M. L., Ferry J. D. Flexibility of myosin rod determined from dilute solution viscoelastic measurements. Biochemistry. 1982 Aug 17;21(17):4064–4073. doi: 10.1021/bi00260a024. [DOI] [PubMed] [Google Scholar]
  32. Karn J., Brenner S., Barnett L. Protein structural domains in the Caenorhabditis elegans unc-54 myosin heavy chain gene are not separated by introns. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4253–4257. doi: 10.1073/pnas.80.14.4253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Kobayasi S., Totsuka T. Electric birefringence of myosin subfragments. Biochim Biophys Acta. 1975 Feb 17;376(2):375–385. doi: 10.1016/0005-2728(75)90029-8. [DOI] [PubMed] [Google Scholar]
  34. Lin S. H., Konishi Y., Denton M. E., Scheraga H. A. Influence of an extrinsic cross-link on the folding pathway of ribonuclease A. Conformational and thermodynamic analysis of cross-linked (lysine7-lysine41)-ribonuclease a. Biochemistry. 1984 Nov 6;23(23):5504–5512. doi: 10.1021/bi00318a019. [DOI] [PubMed] [Google Scholar]
  35. Lu R. C. Identification of a region susceptible to proteolysis in myosin subfragment-2. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2010–2013. doi: 10.1073/pnas.77.4.2010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Lu R. C., Wong A. The amino acid sequence and stability predictions of the hinge region in myosin subfragment 2. J Biol Chem. 1985 Mar 25;260(6):3456–3461. [PubMed] [Google Scholar]
  37. Mak A. S., Smillie L. B., Stewart G. R. A comparison of the amino acid sequences of rabbit skeletal muscle alpha- and beta-tropomyosins. J Biol Chem. 1980 Apr 25;255(8):3647–3655. [PubMed] [Google Scholar]
  38. Mendelson R. A., Morales M. F., Botts J. Segmental flexibility of the S-1 moiety of myosin. Biochemistry. 1973 Jun 5;12(12):2250–2255. doi: 10.1021/bi00736a011. [DOI] [PubMed] [Google Scholar]
  39. 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]
  40. Naylor G. R., Podolsky R. J. X-ray diffraction of strained muscle fibers in rigor. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5559–5563. doi: 10.1073/pnas.78.9.5559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. PAGE S. G., HUXLEY H. E. FILAMENT LENGTHS IN STRIATED MUSCLE. J Cell Biol. 1963 Nov;19:369–390. doi: 10.1083/jcb.19.2.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Reedy M. K., Holmes K. C., Tregear R. T. Induced changes in orientation of the cross-bridges of glycerinated insect flight muscle. Nature. 1965 Sep 18;207(5003):1276–1280. doi: 10.1038/2071276a0. [DOI] [PubMed] [Google Scholar]
  43. SCHELLMAN J. A. The stability of hydrogen-bonded peptide structures in aqueous solution. C R Trav Lab Carlsberg Chim. 1955;29(14-15):230–259. [PubMed] [Google Scholar]
  44. Skolnick J., Holtzer A. Alpha-helix-to-random-coil transitions of two-chain, coiled coils: a theoretical model for the "pretransition" in cysteine-190-cross-linked tropomyosin. Biochemistry. 1986 Oct 7;25(20):6192–6202. doi: 10.1021/bi00368a054. [DOI] [PubMed] [Google Scholar]
  45. Skolnick J. Role of topological constraints in the all-or-none transition of a globular protein model: theory of the helix-coil transition in doubly crosslinked, coiled coils. Biochem Biophys Res Commun. 1985 Jun 28;129(3):848–853. doi: 10.1016/0006-291x(85)91969-2. [DOI] [PubMed] [Google Scholar]
  46. Stafford W. F., 3rd Effect of various anions on the stability of the coiled coil of skeletal muscle myosin. Biochemistry. 1985 Jun 18;24(13):3314–3321. doi: 10.1021/bi00334a036. [DOI] [PubMed] [Google Scholar]
  47. Stein L. A., Schwarz R. P., Jr, Chock P. B., Eisenberg E. Mechanism of actomyosin adenosine triphosphatase. Evidence that adenosine 5'-triphosphate hydrolysis can occur without dissociation of the actomyosin complex. Biochemistry. 1979 Sep 4;18(18):3895–3909. doi: 10.1021/bi00585a009. [DOI] [PubMed] [Google Scholar]
  48. Sutoh K., Chiao Y. C., Harrington W. F. Effect of pH on the cross-bridge arrangement in synthetic myosin filaments. Biochemistry. 1978 Apr 4;17(7):1234–1239. doi: 10.1021/bi00600a016. [DOI] [PubMed] [Google Scholar]
  49. Sutoh K., Sutoh K., Karr T., Harrington W. F. Isolation and physico-chemical properties of a high molecular weight subfragment-2 of myosin. J Mol Biol. 1978 Nov 25;126(1):1–22. doi: 10.1016/0022-2836(78)90276-0. [DOI] [PubMed] [Google Scholar]
  50. Takahashi K. Topography of the myosin molecule as visualized by an improved negative staining method. J Biochem. 1978 Mar;83(3):905–908. doi: 10.1093/oxfordjournals.jbchem.a131988. [DOI] [PubMed] [Google Scholar]
  51. Thomas D. D. Large-scale rotational motions of proteins detected by electron paramagnetic resonance and fluorescence. Biophys J. 1978 Nov;24(2):439–462. doi: 10.1016/S0006-3495(78)85394-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Tsong T. Y., Karr T., Harrington W. F. Rapid helix--coil transitions in the S-2 region of myosin. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1109–1113. doi: 10.1073/pnas.76.3.1109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Wilkie D. R. Muscle as a thermodynamic machine. Ciba Found Symp. 1975;(31):327–339. [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES