Department of Cellular and Molecular Medicine, University of Arizona, Medical Research Building, 1656 East Mabel Street, Tucson, AZ, 85724-5217, USA.
Pflugers Arch. 2014 Mar;466(3):445-50. doi: 10.1007/s00424-013-1432-8. Epub 2014 Jan 19.
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.
肌球蛋白结合蛋白 C（MyBP-C）最初是在从骨骼肌中纯化肌球蛋白时作为杂质发现的。然而，在发现它之后不久，MyBP-C 也被证明与肌动蛋白结合。虽然立即认识到了这种能够将粗丝和细丝交联在一起的蛋白质具有独特的功能意义，但大多数早期研究仍集中在 MyBP-C 与粗丝的相互作用上。这部分是因为 MyBP-C 与粗丝的相互作用可以充分解释 MyBP-C 对肌球蛋白与肌动蛋白相互作用的大多数（但不是全部）影响，部分原因是肌动蛋白结合的特异性不确定。然而，最近的许多研究现在已经证实，MyBP-C 确实可以通过多个结合位点与肌动蛋白结合，其中一些结合位点具有高度特异性。这些相互作用中的许多涉及 MyBP-C 的关键调节域，这些调节域也被报道与肌球蛋白相互作用。在这里，我们回顾了支持 MyBP-C 与肌动蛋白相互作用的现有证据，并根据这些发现讨论了它们在解释 MyBP-C 功能影响方面的作用。我们得出的结论是，MyBP-C 对肌肉收缩的影响可以通过与肌动蛋白的相互作用来解释，也可以通过与肌球蛋白的相互作用来解释。然而，由于表明 MyBP-C 与肌球蛋白或肌动蛋白结合的数据几乎完全来自体外生化研究，因此未来研究的挑战是定义 MyBP-C 在体内与哪个（哪些）结合伴侣相互作用。
