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Structure, sarcomeric organization, and thin filament binding of cardiac myosin-binding protein-C

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Abstract

Myosin-binding protein-C (MyBP-C) is an accessory protein of the myosin filaments of vertebrate striated muscle. In the heart, it plays a key role in modulating contractility in response to β-adrenergic stimulation. Mutations in the cardiac isoform (cMyBP-C) are a leading cause of inherited hypertrophic cardiomyopathy. Understanding cMyBP-C function and its role in disease requires knowledge of the structure of the molecule, its organization in the sarcomere, and its interactions with other sarcomeric proteins. Here we review the main structural features of this modular, elongated molecule and the properties of some of its key domains. We describe observations suggesting that the bulk of the molecule extends perpendicular to the thick filament, enabling it to reach neighboring thin filaments in the sarcomere. We review structural and functional evidence for interaction of its N-terminal domains with actin and how this may modulate thin filament activation. We also discuss the effects that phosphorylation of cMyBP-C has on some of these structural features and how this might relate to cMyBP-C function in the beating heart.

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Acknowledgments

This work was supported by National Institutes of Health grants R01 AR034711 and P01 HL059408 and by British Heart Foundation Programme Grant RG/11/21/29335.

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Authors and Affiliations

  1. Department of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA

    Roger Craig, Kyoung Hwan Lee & Ji Young Mun

  2. Molecular Medicine Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK

    Iratxe Torre & Pradeep K. Luther

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  1. Roger Craig
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  2. Kyoung Hwan Lee
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  4. Iratxe Torre
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Correspondence to Roger Craig.

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Craig, R., Lee, K.H., Mun, J.Y. et al. Structure, sarcomeric organization, and thin filament binding of cardiac myosin-binding protein-C. Pflugers Arch - Eur J Physiol 466, 425–431 (2014). https://doi.org/10.1007/s00424-013-1426-6

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  • DOI: https://doi.org/10.1007/s00424-013-1426-6

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