Myosin binding protein-C: a regulator of actomyosin interaction in striated muscle

Abstract

Myosin-Binding protein-C (MyBP-C) is a family of accessory proteins of striated muscles that contributes to the assembly and stabilization of thick filaments, and regulates the formation of actomyosin cross-bridges, via direct interactions with both thick myosin and thin actin filaments. Three distinct MyBP-C isoforms have been characterized; cardiac, slow skeletal, and fast skeletal. Numerous mutations in the gene for cardiac MyBP-C (cMyBP-C) have been associated with familial hypertrophic cardiomyopathy (FHC) and have led to increased interest in the regulation and roles of the cardiac isoform. This review will summarize our current knowledge on MyBP-C and its role in modulating contractility, focusing on its interactions with both myosin and actin filaments in cardiac and skeletal muscles.

Figure 1

Schematic representation of the three MyBP-C isoforms. White and light grey ovals represent immunoglobulin and fibronectin type-III domains, respectively. The M-motif, flanked by domains C1 and C2 is denoted as a thick black line. Insertions specific to the cardiac isoform and slow variants are shown as dark grey rectangles.

Figure 2

Schematic representation of cardiac MyBP-C, illustrating its domain architecture and known binding partners. Immunoglobulin and fibronectin type III domains are shown as white and grey ovals, respectively. The M-motif is denoted as a dark black line flanked by domains C1 and C2. The cardiac specific insertion within domain C5 is shown as a grey rectangle. Ligands for cMyBP-C are indicated at their sites of interaction.

Figure 3

Schematic representation of the core structure of the skeletal isoforms of MyBP-C, depicting their identified binding partners. For ease of representation, the three novel insertions present in MyBP-C slow are not included in the schematic (for detailed description, please see Figure 1 and [12]). Immunoglobulin and fibronectin type III domains are presented as white and grey ovals, respectively. The M-motif is shown as a dark black line flanked by domains C1 and C2. Ligands for skeletal MyBP-C are denoted at their sites of interaction. Notably, obscurin and FHL1 are specific binding partners of v1, since their interactions depend on the presence of the novel COOH-terminal insertion, which is exclusively carried by v1, in addition to the C10 domain.