Skip to main content
SpringerLink
Log in

N-Terminal Fragment of Cardiac Myosin Binding Protein C Modulates Cooperative Mechanisms of Thin Filament Activation in Atria and Ventricles

  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

Cardiac myosin binding protein C (cMyBP-C) is one of the essential control components of the myosin cross-bridge cycle. The C-terminal part of cMyBP-C is located on the surface of the thick filament, and its N-terminal part interacts with actin, myosin, and tropomyosin, affecting both kinetics of the ATP hydrolysis cycle and lifetime of the cross-bridge, as well as calcium regulation of the actin–myosin interaction, thereby modulating contractile function of myocardium. The role of cMyBP-C in atrial contraction has not been practically studied. We examined effect of the N-terminal C0-C1-m-C2 (C0-C2) fragment of cMyBP-C on actin–myosin interaction using ventricular and atrial myosin in an in vitro motility assay. The C0-C2 fragment of cMyBP-C significantly reduced the maximum sliding velocity of thin filaments on both myosin isoforms and increased the calcium sensitivity of the actin–myosin interaction. The C0-C2 fragment had different effects on the kinetics of ATP and ADP exchange, increasing the affinity of ventricular myosin for ADP and decreasing the affinity of atrial myosin. The effect of the C0-C2 fragment on the activation of the thin filament depended on the myosin isoforms. Atrial myosin activates the thin filament less than ventricular myosin, and the C0-C2 fragment makes these differences in the myosin isoforms more pronounced.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
Fig. 6.

Abbreviations

cMyBP-C:

cardiac myosin-binding protein C

IVMA:

in vitro motility assay

MHC:

myosin heavy chains

RLC:

myosin regulatory light chains

S1 and S2:

myosin subfragments 1 and 2

Tn:

troponin complex

Tpm:

tropomyosin

References

  1. Nagayama, T., Takimoto, E., Sadayappan, S., Mudd, J. O., Seidman, J. G., Robbins, J., Kass, D. A. (2007) Control of in vivo left ventricular [correction] contraction/relaxation kinetics by myosin binding protein C: protein kinase A phosphorylation dependent and independent regulation, Circulation, 20, 2399-2408, https://doi.org/10.1161/CIRCULATIONAHA.107.706523.

    Article  CAS  Google Scholar 

  2. Palmer, B. M., Georgakopoulos, D., Janssen, P. M., Wang, Y., Alpert, N. R., Belardi, D. F., Harris, S. P., Moss, R. L., Burgon, P. G., Seidman, C. E., Seidman, J. G., Maughan, D. W., Kass, D. A. (2004) Role of cardiac myosin binding protein C in sustaining left ventricular systolic stiffening, Circ. Res., 94, 1249-1255, https://doi.org/10.1161/01.RES.0000126898.95550.31.

    Article  CAS  PubMed  Google Scholar 

  3. Janssen, P. M. (2010) Kinetics of cardiac muscle contraction and relaxation are linked and determined by properties of the cardiac sarcomere, Am. J. Physiol. Heart Circ. Physiol., 299, 1092-1099, https://doi.org/10.1152/ajpheart.00417.2010.

    Article  CAS  Google Scholar 

  4. Fazlollahi, F., Santini Gonzalez, J. J., Repas, S. J., Canan, B. D., Billman, G. E., and Janssen, P. M. L. (2021) Contraction-relaxation coupling is unaltered by exercise training and infarction in isolated canine myocardium, J. Gen. Physiol., 153, e202012829, https://doi.org/10.1085/jgp.202012829.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Barefield, D., and Sadayappan, S. (2010) Phosphorylation and function of cardiac myosin binding protein-C in health and disease, J. Mol. Cell. Cardiol., 48, 866-875, https://doi.org/10.1016/j.yjmcc.2009.11.014.

    Article  CAS  PubMed  Google Scholar 

  6. Previs, M. J., Mun, J. Y., Michalek, A. J., Previs, S. B., Gulick, J., Robbins, J., Saber, D. M., and Craig, R. (2016) Phosphorylation and calcium antagonistically tune myosin-binding protein C’s structure and function, Proc. Natl. Acad. Sci. USA, 113, 3239-3244, https://doi.org/10.1073/pnas.1522236113.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  7. Kumar, M., Haghigh, I. K., Kranias, E. G., and Sadayappan, S. (2020) Phosphorylation of cardiac myosin-binding protein-C contributes to calcium homeostasis, J. Biol. Chem., 295, 11275-11291, https://doi.org/10.1074/jbc.RA120.013296.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Huang, X., Torre, I., Chiappi, M., Yin, Z., Vydyanath, A., Cao, S., Raschdorf, O., Beeby, M., Quigley, B., de Tombe, P. P., Liu, J., Morris, E. P., Luther, P. K. (2023) Cryo-electron tomography of intact cardiac muscle reveals myosin binding protein-C linking myosin and actin filaments, J. Muscle Res. Cell Motil., 44, 165-178, https://doi.org/10.1007/s10974-023-09647-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Suay-Corredera, C. and Alegre-Cebollada, J. (2022) The mechanics of the heart: zooming in on hypertrophic cardiomyopathy and cMyBP-C, FEBS Lett., 596, 703-746, https://doi.org/10.1002/1873-3468.14301.

    Article  CAS  PubMed  Google Scholar 

  10. Dutta, D., Nguyen, V., Campbell, K. S., Padrón, R., and Craig, R. (2023) Cryo-EM structure of the human cardiac myosin filament, Nature, 623, 853-862, https://doi.org/10.1038/s41586-023-06691-4.

    Article  CAS  PubMed  ADS  Google Scholar 

  11. Gruen, M., and Gautel, M. (1999) Mutations in β-myosin S2 that cause familial hypertrophic cardiomyopathy (FHC) abolish the interaction with the regulatory domain of myosin binding protein-C, J. Mol. Biol., 286, 933-949, https://doi.org/10.1006/jmbi.1998.2522.

    Article  CAS  PubMed  Google Scholar 

  12. Kulikovskaya, I., McClellan, G., Flavigny, J., Carrier, L., and Winegrad, S. (2003) Effect of MyBP-C binding to actin on contractility in heart muscle, J. Gen. Physiol., 122, 761-774, https://doi.org/10.1085/jgp.200308941.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Whitten, A. E., Jeffries, C. M., Harris, S. P., and Trewhella, J. (2008) Cardiac myosin-binding protein C decorates F-actin: implications for cardiac function, Proc. Natl Acad. Sci. USA, 105, 18360-18365, https://doi.org/10.1073/pnas.0808903105.

    Article  PubMed  PubMed Central  ADS  Google Scholar 

  14. Shaffer, J. F., Kensler, R. W., and Harris, S. P. (2009) The myosin-binding protein C motif binds to F-actin in a phosphorylation-sensitive manner, J. Biol. Chem., 284, 12318-12327, https://doi.org/10.1074/jbc.M808850200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Orlova, A., Galkin, V. E., Jeffries, C. M., Egelman, E. H., and Trewhella, J. (2011) The N-terminal domains of myosin binding protein C can bind polymorphically to F-actin, J. Mol. Biol., 412, 379-386, https://doi.org/10.1016/j.jmb.2011.07.056.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bhuiyan, M. S., McLendon, P., James, J., Osinska, H., Gulick, J., Bhandary, B., Lorenz, J. N., Robbins, J. (2016) In vivo definition of cardiac myosin-binding protein C’s critical interactions with myosin, Pflugers Arch., 468, 1685-1695, https://doi.org/10.1007/s00424-016-1873-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Tamborrini, D., Wang, Z., Wagner, T., Tacke, S., Stabrin, M., Grange, M., Kho, A. L., Rees, M., Bennett, P., Gautel, M., Raunser, S. (2023) Structure of the native myosin filament in the relaxed cardiac sarcomere, Nature, 623, 863-871, https://doi.org/10.1038/s41586-023-06690-5.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  18. Ponnam, S., and Kampourakis, T. (2022) Microscale thermophoresis suggests a new model of regulation of cardiac myosin function via interaction with cardiac myosin-binding protein C, J. Biol. Chem., 298, 101485, https://doi.org/10.1016/j.jbc.2021.101485.

    Article  CAS  PubMed  Google Scholar 

  19. Doh, C. Y., Bharambe, N., Holmes, J. B., Dominic, K. L., Swanberg, C. E., Mamidi, R., Chen, Y., Bandyopadhyay, S., Ramachandran, R., Stelzer, J. E. (2022) Molecular characterization of linker and loop-mediated structural modulation and hinge motion in the C4-C5 domains of cMyBPC, J. Struct. Biol., 214, 107856, https://doi.org/10.1016/j.jsb.2022.107856.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Sadayappan, S., and de Tombe, P. P. (2012) Cardiac myosin binding protein-C: redefining its structure and function, Biophys. Rev., 4, 93-106, https://doi.org/10.1007/s12551-012-0067-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Walcott, S., Docken, S., and Harris, S. P. (2015) Effects of cardiac Myosin binding protein-C on actin motility are explained with a drag-activation-competition model, Biophys. J., 108, 10-13, https://doi.org/10.1016/j.bpj.2014.11.1852.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  22. Colson, B. A., Thompson, A. R., Espinoza-Fonseca, L. M., and Thomas, D. D. (2016) Site-directed spectroscopy of cardiac myosin-binding protein C reveals effects of phosphorylation on protein structural dynamics, Proc. Natl. Acad. Sci. USA, 113, 3233-3238, https://doi.org/10.1073/pnas.1521281113.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  23. Moss, R. L. (2016) Cardiac myosin-binding protein C: a protein once at loose ends finds its regulatory groove, Proc. Natl. Acad. Sci. USA, 113, 3133-3135, https://doi.org/10.1073/pnas.1602568113.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  24. Risi, C., Belknap, B., Forgacs-Lonart, E., Harris, S. P., Schröder, G. F., White, H. D., and Galkin, V. E. (2018) N-Terminal domains of cardiac myosin binding protein C cooperatively activate the thin filament, Structure, 26, 1604-1611.e4, https://doi.org/10.1016/j.str.2018.08.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Harris, S. P., Belknap, B., Van Sciver, R. E., White, H. D., and Galkin, V. E. (2016) C0 and C1 N-terminal Ig domains of myosin binding protein C exert different effects on thin filament activation, Proc. Natl. Acad. Sci. USA, 113, 1558-1563, https://doi.org/10.1073/pnas.1518891113.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  26. Mun, J. Y., Previs, M. J., Yu, H. Y., Gulick, J., Tobacman, L. S., Beck Previs, S., Robbins, J., Warshaw, D. M., and Craig, R. (2014) Myosin-binding protein C displaces tropomyosin to activate cardiac thin filaments and governs their speed by an independent mechanism, Proc. Natl. Acad. Sci. USA, 111, 2170-2175, https://doi.org/10.1073/pnas.1316001111.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  27. Inchingolo, A. V., Previs, S. B., Previs, M. J., Warshaw, D. M., and Kad, N. M. (2019) Revealing the mechanism of how cardiac myosin-binding protein C N-terminal fragments sensitize thin filaments for myosin binding, Proc. Natl. Acad. Sci. USA, 116, 6828-6835, https://doi.org/10.1073/pnas.1816480116.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  28. Stelzer, J. E., Fitzsimons, D. P., and Moss, R. L. (2006) Ablation of myosin-binding protein-C accelerates force development in mouse myocardium, Biophys. J., 90, 4119-4127, https://doi.org/10.1529/biophysj.105.078147.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  29. Stelzer, J. E., Patel, J. R., and Moss, R. L. (2006) Protein kinase A-mediated acceleration of the stretch activation response in murine skinned myocardium is eliminated by ablation of cMyBP-C, Circ Res., 99, 884-890, https://doi.org/10.1161/01.RES.0000245191.34690.66.

    Article  CAS  PubMed  Google Scholar 

  30. Napierski, N. C., Granger, K., Langlais, P. R., Moran, H. R., Strom, J., Touma, K., and Harris, S. P. (2020) A novel “Cut and Paste” method for in situ replacement of cMyBP-C reveals a new role for cMyBP-C in the regulation of contractile oscillations, Circ. Res., 126, 737-749, https://doi.org/10.1161/CIRCRESAHA.119.315760.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Razumova, M. V., Bezold, K. L., Tu, A. Y., Regnier, M., and Harris, S. P. (2008) Contribution of the myosin binding protein C motif to functional effects in permeabilized rat trabeculae, J. Gen. Physiol., 132, 575-585, https://doi.org/10.1085/jgp.200810013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Razumova, M. V., Shaffer, J. F., Tu, A. Y., Flint, G. V., Regnier, M., and Harris, S. P. (2006) Effects of the N-terminal domains of myosin binding protein-C in an in vitro motility assay: evidence for long-lived cross-bridges, J. Biol. Chem., 281, 35846-35854, https://doi.org/10.1074/jbc.M606949200.

    Article  CAS  PubMed  Google Scholar 

  33. Saber, W., Begin, K. J., Warshaw, D. M., and VanBuren, P. (2008) Cardiac myosin binding protein-C modulates actomyosin binding and kinetics in the in vitro motility assay, J. Mol. Cell Cardiol., 44, 1053-1061, https://doi.org/10.1016/j.yjmcc.2008.03.012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Shchepkin, D. V., Kopylova, G. V., Nikitina, L. V., Katsnelson, L. B., and Bershitsky, S. Y. (2010) Effects of cardiac myosin binding protein-C on the regulation of interaction of cardiac myosin with thin filament in an in vitro motility assay, Biochem. Biophys. Res. Commun., 401, 159-163, https://doi.org/10.1016/j.bbrc.2010.09.040.

    Article  CAS  PubMed  Google Scholar 

  35. Chandler, J., Treacy, C., Ameer-Beg, S., Ehler, E., Irving, M., and Kampourakis, T. (2012) In situ FRET-based localization of the N terminus of myosin binding protein-C in heart muscle cells, Proc. Natl. Acad. Sci. USA, 120, e2222005120, https://doi.org/10.1073/pnas.2222005120.

    Article  CAS  Google Scholar 

  36. Nelson, S., Beck-Previs, S., Sadayappan, S., Tong, C., and Warshaw, D. M. (2023) Myosin-binding protein C stabilizes, but is not the sole determinant of SRX myosin in cardiac muscle, J. Gen. Physiol., 155, e202213276, https://doi.org/10.1085/jgp.202213276.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Moss, R. L., Fitzsimons, D. P., and Ralphe, J. C. (2015) Cardiac MyBP-C regulates the rate and force of contraction in mammalian myocardium, Circ. Res., 116, 183-192, https://doi.org/10.1161/CIRCRESAHA.116.300561.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. De Lange, W. J., Grimes, A. C., Hegge, L. F., and Ralphe, J. C. (2013) Ablation of cardiac myosin-binding protein-C accelerates contractile kinetics in engineered cardiac tissue, J. Gen. Physiol., 141, 73-84, https://doi.org/10.1085/jgp.201210837.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. McNamara, J. W., Singh, R. R., and Sadayappan, S. (2019) Cardiac myosin binding protein-C phosphorylation regulates the super-relaxed state of myosin, Proc. Natl. Acad. Sci. USA, 116, 11731-11736, https://doi.org/10.1073/pnas.1821660116.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  40. Tanner, B. C., Wang, Y., Robbins, J., and Palmer, B. M. (2014) Kinetics of cardiac myosin isoforms in mouse myocardium are affected differently by presence of myosin binding protein-C, J. Muscle Res. Cell Motil., 35, 267-278, https://doi.org/10.1007/s10974-014-9390-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Tanner, B. C. W., Previs, M. J., Wang, Y., Robbins, J., and Palmer, B. M. (2021) Cardiac myosin binding protein-C phosphorylation accelerates β-cardiac myosin detachment rate in mouse myocardium, Am. J. Physiol. Heart Circ. Physiol., 320, H1822-H1835, https://doi.org/10.1152/ajpheart.00673.2020.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Wang, L., Sadayappan, S., and Kawai, M. (2014) Cardiac myosin binding protein C phosphorylation affects cross-bridge cycle’s elementary steps in a site-specific manner, PLoS One, 9, e113417, https://doi.org/10.1371/journal.pone.0113417.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  43. Gordon, A. M., Homsher, E., Regnier, M. (2000) Regulation of contraction in striated muscle, Physiol. Rev., 80, 853-924, https://doi.org/10.1152/physrev.2000.80.2.853.

    Article  CAS  PubMed  Google Scholar 

  44. Gorga, J. A., Fishbaugher, D. E., and VanBuren, P. (2003) Activation of the calcium-regulated thin filament by myosin strong binding, Biophys. J., 85, 2484-2491, https://doi.org/10.1016/S0006-3495(03)74671-2.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  45. Narolska, N. A., Eiras, S., van Loon, R. B., Boontje, N. M., Zaremba, R., Spiegelen Berg, S. R., Stooker, W., Huybregts, M. A., Visser, F. C., van der Velden, J., and Stienen, G. J. (2005) Myosin heavy chain composition and the economy of contraction in healthy and diseased human myocardium, J. Muscle Res. Cell Motil., 26, 39-48, https://doi.org/10.1007/s10974-005-9005-x.

    Article  CAS  PubMed  Google Scholar 

  46. Morano, I., (1999) Tuning the human heart molecular motors by myosin light chains, J. Mol. Med., 77, 544-555, https://doi.org/10.1007/s001099900031.

    Article  CAS  PubMed  Google Scholar 

  47. Yamashita, H., Sugiura, S., Fujita, H., Yasuda, Si, Nagai, R., Saeki, Y., Sunagawa, K., and Sugi, H. (2003) Myosin light chain isoforms modify force-generating ability of cardiac myosin by changing the kinetics of actin-myosin interaction, Cardiovasc. Res., 60, 580-588, https://doi.org/10.1016/j.cardiores.2003.09.011.

    Article  CAS  PubMed  Google Scholar 

  48. Shchepkin, D. V., Nikitina, L. V., Bershitsky, S. Y., and Kopylova, G. V. (2017) The isoforms of α-actin and myosin affect the Ca2+ regulation of the actin-myosin interaction in the heart, Biochem. Biophys. Res. Commun., 490, 324-329, https://doi.org/10.1016/j.bbrc.2017.06.043.

    Article  CAS  PubMed  Google Scholar 

  49. Kopylova, G., Nabiev, S., Nikitina, L., Shchepkin, D., and Bershitsky, S. (2016) The properties of the actin-myosin interaction in the heart muscle depend on the isoforms of myosin but not of α-actin, Biochem. Biophys. Res. Commun., 476, 648-653, https://doi.org/10.1016/j.bbrc.2016.06.013.

    Article  CAS  PubMed  Google Scholar 

  50. Kopylova, G. V., Berg, V. Y., Kochurova, A. M., Matyushenko, A. M., Bershitsky, S. Y., and Shchepkin, D. V. (2022) The effects of the tropomyosin cardiomyopathy mutations on the calcium regulation of actin-myosin interaction in the atrium and ventricle differ, Biochem. Biophys. Res. Commun., 588, 29-33, https://doi.org/10.1016/j.bbrc.2021.12.051.

    Article  CAS  PubMed  Google Scholar 

  51. Pohlmann, L., Kröger, I., Vignier, N., Schlossarek, S., Krämer, E., Coirault, C., Sultan, K. R., El-Armouche, A., Winegrad, S., Eschenhagen, T., and Carrier, L. (2007) Cardiac myosin-binding protein C is required for complete relaxation in intact myocytes, Circ. Res., 101, 928-938, https://doi.org/10.1161/CIRCRESAHA.107.158774.

    Article  CAS  PubMed  Google Scholar 

  52. El-Armouche, A., Boknik, P., Eschenhagen, T., Carrier, L., Knaut, M., Ravens, U., and Dobrev, D. (2006) Molecular determinants of altered Ca2+ handling in human chronic atrial fibrillation, Circulation, 114, 670-680, https://doi.org/10.1161/CIRCULATIONAHA.106.636845.

    Article  CAS  PubMed  Google Scholar 

  53. Wakili, R., Yeh, Y. H., Yan Qi, X., Greiser, M., Chartier, D., Nishida, K., Maguy, A., Villeneuve, L.-R., Boknik, P., Voigt, N., Krysiak, J., Kääb, S., Ravens, U., Linke, W. A., Stienen, G. J. M., Shi, Y., Tardif, J.-C., Schotten, U., Dobrev, D., Nattel, S. (2010) Multiple potential molecular contributors to atrial hypocontractility caused by atrial tachycardia remodeling in dogs, Circ. Arrhythm. Electrophysiol., 3, 530-541, https://doi.org/10.1161/CIRCEP.109.933036.

    Article  CAS  PubMed  Google Scholar 

  54. Butova, X., Myachina, T., Simonova, R., Kochurova, A., Mukhlynina, E., Kopylova, G., Shchepkin, D., and Khokhlova, A. (2023) The inter-chamber differences in the contractile function between left and right atrial cardiomyocytes in atrial fibrillation in rats, Front. Cardiovasc. Med., 10, 1203093, https://doi.org/10.3389/fcvm.2023.1203093.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Margossian, S. S., and Lowey, S. (1982) Preparation of myosin and its subfragments from rabbit skeletal muscle, Methods Enzymol., 85, 55-71, https://doi.org/10.1016/0076-6879(82)85009-x.

    Article  CAS  PubMed  Google Scholar 

  56. Reiser, P. J., and Kline, W. O. (1998) Electrophoretic separation and quantitation of cardiac myosin heavy chain isoforms in eight mammalian species, Am. J. Physiol., 274, 1048-1053, https://doi.org/10.1152/ajpheart.1998.274.3.H1048.

    Article  Google Scholar 

  57. Pardee, J. D., and Spudich, J. A. (1982) Purification of muscle actin, Methods Enzymol., 85, 164-181, https://doi.org/10.1016/0076-6879(82)85020-9.

    Article  CAS  PubMed  Google Scholar 

  58. Mashanov, G. I., and Molloy, J. E. (2007) Automatic detection of single fluorophores in live cells, Biophys. J., 92, 2199-2211, https://doi.org/10.1529/biophysj.106.081117.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  59. Deacon, J. C., Bloemink, M. J., Rezavandi, H., Geeves, M. A., and Leinwand, L. A. (2012) Identification of functional differences between recombinant human α and β cardiac myosin motors, Cell. Mol. Life Sci., 69, 2261-2277, https://doi.org/10.1007/s00018-012-0927-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Walklate, J., Ferrantini, C., Johnson, C. A., Tesi, C., Poggesi, C., and Geeves, M. A. (2021) Alpha and beta myosin isoforms and human atrial and ventricular contraction, Cell. Mol. Life Sci., 78, 7309-7337, https://doi.org/10.1007/s00018-021-03971-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Homsher, E., Nili, M., Chen, I. Y., and Tobacman, L. S. (2003) Regulatory proteins alter nucleotide binding to acto-myosin of sliding filaments in motility assays, Biophys. J., 85, 1046-1052, https://doi.org/10.1016/S0006-3495(03)74543-3.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  62. Tian, R., Christe, M. E., Spindler, M., Hopkins, J. C., Halow, J. M., Camacho, S. A., and Ingwall, J. S. (1997) Role of MgADP in the development of diastolic dysfunction in the intact beating rat heart, J. Clin. Invest., 99, 745-751, https://doi.org/10.1172/JCI119220.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Sequeira, V., Najafi, A., McConnell, M., Fowler, E. D., Bollen, I. A., Wüst, R. C., dos Remedios, C., Helmes, M., White, E., Stienen, G. J., Tardiff, J., Kuster, D. W., and van der Velden, J. (2015) Synergistic role of ADP and Ca2+ in diastolic myocardial stiffness, J. Physiol., 593, 3899-3916, https://doi.org/10.1113/JP270354.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Sugiura, S., Kobayakawa, N., Fujita, H., Yamashita, H., Momomura, S., Chaen, S., Omata, M., and Sugi, H. (1998) Comparison of unitary displacements and forces between 2 cardiac myosin isoforms by the optical trap technique: molecular basis for cardiac adaptation, Circ. Res., 82, 1029-1034, https://doi.org/10.1161/01.res.82.10.1029.

    Article  CAS  PubMed  Google Scholar 

  65. Palmiter, K. A., Tyska, M. J., Dupuis, D. E., Alpert, N. R., and Warshaw, D. M. (1999) Kinetic differences at the single molecule level account for the functional diversity of rabbit cardiac myosin isoforms, J. Physiol., 519, 669-678, https://doi.org/10.1111/j.1469-7793.1999.0669n.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Ratti, J., Rostkova, E., Gautel, M., and Pfuhl, M. (2011) Structure and interactions of myosin-binding protein C domain C0: cardiac-specific regulation of myosin at its neck? J. Biol. Chem., 286, 12650-12658, https://doi.org/10.1074/jbc.M110.156646.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Nabiev, S. R., Kopylova, G. V., and Shchepkin, D. V. (2019) The effect of cardiac myosin-binding protein c on calcium regulation of the actin–myosin interaction depends on myosin light chain isoforms, Mol. Biophys., 64, 690-693, https://doi.org/10.1134/S000635091905018X.

    Article  CAS  Google Scholar 

  68. McKillop, D. F., and Geeves, M. A. (1993) Regulation of the interaction between actin and myosin subfragment 1: evidence for three states of the thin filament, Biophys. J., 65, 693-701, https://doi.org/10.1016/S0006-3495(93)81110-X.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  69. Matyushenko, A. M., Shchepkin, D. V., Kopylova, G. V., Bershitsky, S. Y., and Levitsky, D. I. (2020) Unique functional properties of slow skeletal muscle tropomyosin, Biochimie, 174, 1-8, https://doi.org/10.1016/j.biochi.2020.03.013.

    Article  CAS  PubMed  Google Scholar 

  70. Papp, Z., Szabó, A., Barends, J. P., and Stienen, G. J. (2002) The mechanism of the force enhancement by MgADP under simulated ischaemic conditions in rat cardiac myocytes, J. Physiol., 543, 177-189, https://doi.org/10.1113/jphysiol.2002.022145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Cha, Y. M., Dzeja, P. P., Shen, W. K., Jahangir, A., Hart, C. Y., Terzic, A., and Redfield, M. M. (2003) Failing atrial myocardium: energetic deficits accompany structural remodeling and electrical instability, Am. J. Physiol. Heart Circ. Physiol., 284, H1313-H1320, https://doi.org/10.1152/ajpheart.00337.2002.

    Article  CAS  PubMed  Google Scholar 

  72. Shimura, D., Nakai, G., Jiao, Q., Osanai, K., Kashikura, K., Endo, K., Soga, T., Goda, N., and Minamisawa, S. (2012) Metabolomic profiling analysis reveals chamber-dependent metabolite patterns in the mouse heart, Am. J. Physiol. Heart Circ. Physiol., 305, H494-H505, https://doi.org/10.1152/ajpheart.00867.2012.

    Article  CAS  Google Scholar 

Download references

Funding

The work was carried out with financial support from the Russian Science Foundation (grant no. 22-14-00174).

Author information

Authors and Affiliations

  1. Institute of Immunology and Physiology, Russian Academy of Sciences, 620049, Yekaterinburg, Russia

    Anastasia M. Kochurova, Evgenia A. Beldiia, Sergey Y. Bershitsky, Galina V. Kopylova & Daniil V. Shchepkin

  2. Ural Federal University, 620002, Ekaterinburg, Russia

    Evgenia A. Beldiia

  3. Bach Institute of Biochemistry, Research Center of Biotechnology, Russian Academy of Sciences, 119071, Moscow, Russia

    Victoria V. Nefedova, Daria S. Yampolskaya & Alexander M. Matyushenko

  4. Department of Biochemistry, Faculty of Biology, Lomonosov Moscow State University, 119234, Moscow, Russia

    Natalia S. Ryabkova

  5. HyTest Ltd., 20520, Turku, Finland

    Natalia S. Ryabkova

Authors
  1. Anastasia M. Kochurova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Evgenia A. Beldiia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Victoria V. Nefedova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Natalia S. Ryabkova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Daria S. Yampolskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alexander M. Matyushenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sergey Y. Bershitsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Galina V. Kopylova
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Daniil V. Shchepkin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

S.Y.B., G.V.K., and D.V.S. concept and management of the work; A.M.K., E.A.B., G.V.K., and D.V.S. conducting experiments in the in vitro motility assay; A.M.K., E.A.B., and G.V.K. processing the experimental data; N.S.R., D.S.Y., A.M.M., and V.V.N. performing protein expression; G.V.K. and D.V.S. writing the article; A.M.M., S.Y.B., G.V.K., and D.V.S. editing final version of the article. All authors approved final version of the article.

Corresponding author

Correspondence to Daniil V. Shchepkin.

Ethics declarations

This work does not contain any studies involving human and animal subjects. The authors of this work declare that they have no conflicts of interest.

Additional information

Publisher’s Note. Pleiades Publishing remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kochurova, A.M., Beldiia, E.A., Nefedova, V.V. et al. N-Terminal Fragment of Cardiac Myosin Binding Protein C Modulates Cooperative Mechanisms of Thin Filament Activation in Atria and Ventricles. Biochemistry Moscow 89, 116–129 (2024). https://doi.org/10.1134/S0006297924010073

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297924010073

Keywords

Search

Navigation