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Earning stripes: myosin binding protein-C interactions with actin

Abstract

Myosin binding protein-C (MyBP-C) was first discovered as an impurity during the purification of myosin from skeletal muscle. However, soon after its discovery, MyBP-C was also shown to bind actin. While the unique functional implications for a protein that could cross-link thick and thin filaments together were immediately recognized, most early research nonetheless focused on interactions of MyBP-C with the thick filament. This was in part because interactions of MyBP-C with the thick filament could adequately explain most (but not all) effects of MyBP-C on actomyosin interactions and in part because the specificity of actin binding was uncertain. However, numerous recent studies have now established that MyBP-C can indeed bind to actin through multiple binding sites, some of which are highly specific. Many of these interactions involve critical regulatory domains of MyBP-C that are also reported to interact with myosin. Here we review current evidence supporting MyBP-C interactions with actin and discuss these findings in terms of their ability to account for the functional effects of MyBP-C. We conclude that the influence of MyBP-C on muscle contraction can be explained equally well by interactions with actin as by interactions with myosin. However, because data showing that MyBP-C binds to either myosin or actin has come almost exclusively from in vitro biochemical studies, the challenge for future studies is to define which binding partner(s) MyBP-C interacts with in vivo.

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Correspondence to Samantha P. Harris.

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This article is published as part of the Special Issue on Cardiac Myosin Binding Protein-C as a Central Target of Cardiac Sarcomere Signaling.

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van Dijk, S.J., Bezold, K.L. & Harris, S.P. Earning stripes: myosin binding protein-C interactions with actin. Pflugers Arch - Eur J Physiol 466, 445–450 (2014). https://doi.org/10.1007/s00424-013-1432-8

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  • DOI: https://doi.org/10.1007/s00424-013-1432-8

Keywords

  • Myosin
  • Actin
  • Myosin binding protein-C
  • Sarcomere
  • Muscle