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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Jun 1;90(11):5252–5256. doi: 10.1073/pnas.90.11.5252

Structural changes in the actomyosin cross-bridges associated with force generation.

B Brenner 1, L C Yu 1
PMCID: PMC46694  PMID: 8506374

Abstract

It is generally thought that to generate active force in muscle, myosin heads (cross-bridges) that are attached to actin undergo large-scale conformational changes. However, evidence for conformational changes of the attached cross-bridges associated with force generation has been ambiguous. In this study, we took advantage of the recent observation that cross-bridges that are weakly attached to actin in a relaxed muscle are apparently in attached preforce-generating states. The experimental conditions were chosen such that there were large fractions of cross-bridges attached under relaxing and activating conditions, and high-resolution equatorial x-ray diffraction patterns obtained under these conditions were compared. Changes brought about by activation in the two innermost intensities, I10 and I11, did not follow the familiar reciprocal changes. Instead, there was almost no change in I11, whereas I10 decreased by 34%. Together with the changes found in the higher-order reflections, the results suggest that the structure of the attached force-generating cross-bridges differs from that of the weakly bound, preforce-generating cross-bridges and possibly also differs from that of the cross-bridges in rigor. These observations support the concept that force generation involves a transition between distinct structural states of the actomyosin cross-bridges.

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Selected References

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  1. Brenner B., Chalovich J. M., Greene L. E., Eisenberg E., Schoenberg M. Stiffness of skinned rabbit psoas fibers in MgATP and MgPPi solution. Biophys J. 1986 Oct;50(4):685–691. doi: 10.1016/S0006-3495(86)83509-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brenner B., Schoenberg M., Chalovich J. M., Greene L. E., Eisenberg E. Evidence for cross-bridge attachment in relaxed muscle at low ionic strength. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7288–7291. doi: 10.1073/pnas.79.23.7288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brenner B. Technique for stabilizing the striation pattern in maximally calcium-activated skinned rabbit psoas fibers. Biophys J. 1983 Jan;41(1):99–102. doi: 10.1016/S0006-3495(83)84411-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brenner B., Yu L. C., Chalovich J. M. Parallel inhibition of active force and relaxed fiber stiffness in skeletal muscle by caldesmon: implications for the pathway to force generation. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5739–5743. doi: 10.1073/pnas.88.13.5739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cecchi G., Griffiths P. J., Bagni M. A., Ashley C. C., Maeda Y. Time-resolved changes in equatorial x-ray diffraction and stiffness during rise of tetanic tension in intact length-clamped single muscle fibers. Biophys J. 1991 Jun;59(6):1273–1283. doi: 10.1016/S0006-3495(91)82342-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chalovich J. M., Chock P. B., Eisenberg E. Mechanism of action of troponin . tropomyosin. Inhibition of actomyosin ATPase activity without inhibition of myosin binding to actin. J Biol Chem. 1981 Jan 25;256(2):575–578. [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Harford J. J., Squire J. M. Evidence for structurally different attached states of myosin cross-bridges on actin during contraction of fish muscle. Biophys J. 1992 Aug;63(2):387–396. doi: 10.1016/S0006-3495(92)81613-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hibberd M. G., Trentham D. R. Relationships between chemical and mechanical events during muscular contraction. Annu Rev Biophys Biophys Chem. 1986;15:119–161. doi: 10.1146/annurev.bb.15.060186.001003. [DOI] [PubMed] [Google Scholar]
  10. Huxley H. E., Kress M. Crossbridge behaviour during muscle contraction. J Muscle Res Cell Motil. 1985 Apr;6(2):153–161. doi: 10.1007/BF00713057. [DOI] [PubMed] [Google Scholar]
  11. Huxley H. E. Structural difference between resting and rigor muscle; evidence from intensity changes in the lowangle equatorial x-ray diagram. J Mol Biol. 1968 Nov 14;37(3):507–520. doi: 10.1016/0022-2836(68)90118-6. [DOI] [PubMed] [Google Scholar]
  12. Irving M., Lombardi V., Piazzesi G., Ferenczi M. A. Myosin head movements are synchronous with the elementary force-generating process in muscle. Nature. 1992 May 14;357(6374):156–158. doi: 10.1038/357156a0. [DOI] [PubMed] [Google Scholar]
  13. Irving T. C., Millman B. M. Changes in thick filament structure during compression of the filament lattice in relaxed frog sartorius muscle. J Muscle Res Cell Motil. 1989 Oct;10(5):385–394. doi: 10.1007/BF01758435. [DOI] [PubMed] [Google Scholar]
  14. Kabsch W., Mannherz H. G., Suck D., Pai E. F., Holmes K. C. Atomic structure of the actin:DNase I complex. Nature. 1990 Sep 6;347(6288):37–44. doi: 10.1038/347037a0. [DOI] [PubMed] [Google Scholar]
  15. Kraft T., Yu L. C., Kuhn H. J., Brenner B. Effect of Ca2+ on weak cross-bridge interaction with actin in the presence of adenosine 5'-[gamma-thio]triphosphate). Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11362–11366. doi: 10.1073/pnas.89.23.11362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kress M., Huxley H. E., Faruqi A. R., Hendrix J. Structural changes during activation of frog muscle studied by time-resolved X-ray diffraction. J Mol Biol. 1986 Apr 5;188(3):325–342. doi: 10.1016/0022-2836(86)90158-0. [DOI] [PubMed] [Google Scholar]
  17. Matsubara I., Yagi N., Hashizume H. Use of an X-ray television for diffraction of the frog striated muscle. Nature. 1975 Jun 26;255(5511):728–729. doi: 10.1038/255728a0. [DOI] [PubMed] [Google Scholar]
  18. Matsuda T., Podolsky R. J. X-ray evidence for two structural states of the actomyosin cross-bridge in muscle fibers. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2364–2368. doi: 10.1073/pnas.81.8.2364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pringle J. W. The contractile mechanism of insect fibrillar muscle. Prog Biophys Mol Biol. 1967;17:1–60. doi: 10.1016/0079-6107(67)90003-x. [DOI] [PubMed] [Google Scholar]
  20. Squire J. M., Podolsky R. J., Barry J. S., Yu L. C., Brenner B. X-ray diffraction testing for weak-binding crossbridges in relaxed bony fish muscle fibres at low ionic strength. J Struct Biol. 1991 Dec;107(3):221–226. doi: 10.1016/1047-8477(91)90047-z. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Trus B. L., Steven A. C., McDowall A. W., Unser M., Dubochet J., Podolsky R. J. Interactions between actin and myosin filaments in skeletal muscle visualized in frozen-hydrated thin sections. Biophys J. 1989 Apr;55(4):713–724. doi: 10.1016/S0006-3495(89)82870-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wagner P. D., Giniger E. Calcium-sensitive binding of heavy meromyosin to regulated actin in the presence of ATP. J Biol Chem. 1981 Dec 25;256(24):12647–12650. [PubMed] [Google Scholar]
  24. Xu S. G., Kress M., Huxley H. E. X-ray diffraction studies of the structural state of crossbridges in skinned frog sartorius muscle at low ionic strength. J Muscle Res Cell Motil. 1987 Feb;8(1):39–54. doi: 10.1007/BF01767263. [DOI] [PubMed] [Google Scholar]
  25. Xu S., Brenner B., Yu L. C. State-dependent radial elasticity of attached cross-bridges in single skinned fibres of rabbit psoas muscle. J Physiol. 1993 Jun;465:749–765. doi: 10.1113/jphysiol.1993.sp019704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Yu L. C. Analysis of equatorial x-ray diffraction patterns from skeletal muscle. Biophys J. 1989 Mar;55(3):433–440. doi: 10.1016/S0006-3495(89)82837-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Yu L. C., Brenner B. Structures of actomyosin crossbridges in relaxed and rigor muscle fibers. Biophys J. 1989 Mar;55(3):441–453. doi: 10.1016/S0006-3495(89)82838-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Yu L. C., Steven A. C., Naylor G. R., Gamble R. C., Podolsky R. J. Distribution of mass in relaxed frog skeletal muscle and its redistribution upon activation. Biophys J. 1985 Mar;47(3):311–321. doi: 10.1016/S0006-3495(85)83921-7. [DOI] [PMC free article] [PubMed] [Google Scholar]

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