MYBPC - myosin binding protein C | Elisa - Clia - Antibody - Protein

Background

Myosin binding protein C (MYBPC) is a crucial component of the sarcomere, the fundamental unit of muscle contraction in striated muscles. This protein family is encoded by the MYBPC genes and plays a vital role in the regulation of muscle contraction and the structural integrity of the sarcomere. There are three main isoforms of MYBPC: MYBPC1 (slow skeletal), MYBPC2 (fast skeletal), and MYBPC3 (cardiac). Each isoform is specifically expressed in different types of muscle fibers, reflecting the specialized functions they serve in muscle physiology.

MYBPC was first discovered in the 1970s as a component of the thick filament in cardiac muscle. Subsequent research has revealed its presence in both cardiac and skeletal muscles, underscoring its importance in muscle function. MYBPC proteins are essential for normal muscle function and development, and mutations in the MYBPC3 gene, in particular, are a leading cause of hypertrophic cardiomyopathy (HCM), a common inherited cardiac disorder.

Protein Structure

MYBPC proteins are large, multidomain proteins that interact with both thick (myosin) and thin (actin) filaments within the sarcomere. The structure of MYBPC can be broken down into several key domains:

1. N-terminal Domains: The N-terminus contains several immunoglobulin (Ig) and fibronectin type III (Fn3) domains. These domains mediate interactions with myosin, actin, and titin, a giant protein that contributes to the elastic properties of the sarcomere.
2. C-terminal Domains: The C-terminus also contains Ig and Fn3 domains, which anchor MYBPC to the thick filament. The C-terminal region is crucial for the structural stability of the sarcomere.
3. Phosphorylation Sites: MYBPC contains several phosphorylation sites, particularly in the cardiac isoform. Phosphorylation of these sites by kinases such as protein kinase A (PKA) and protein kinase C (PKC) modulates MYBPC's interaction with other sarcomeric proteins and regulates muscle contraction.

The specific arrangement of these domains and their interactions with sarcomeric components allow MYBPC to perform its regulatory functions in muscle contraction and relaxation.

Classification and Subtypes

MYBPC proteins are classified into three main isoforms based on their expression patterns in different muscle types:

1. MYBPC1 (Slow Skeletal): Expressed in slow-twitch skeletal muscle fibers, which are involved in sustained, endurance-type activities.
2. MYBPC2 (Fast Skeletal): Found in fast-twitch skeletal muscle fibers, which are responsible for rapid, powerful contractions.
3. MYBPC3 (Cardiac): Present in cardiac muscle, where it plays a critical role in the regulation of heart muscle contraction and relaxation.

Each isoform has unique regulatory mechanisms and functions tailored to the specific demands of the muscle type in which it is expressed.

Function and Biological Significance

MYBPC proteins serve several essential functions in muscle cells:

1. Regulation of Contraction: MYBPC modulates the interaction between myosin and actin filaments, influencing the strength and speed of muscle contraction. Phosphorylation of MYBPC3, for instance, alters its binding properties, thereby regulating cardiac contractility.
2. Structural Integrity: MYBPC contributes to the structural organization of the sarcomere, ensuring proper alignment and stability of thick filaments. This structural role is critical for the mechanical function of muscles.
3. Signal Transduction: Through its interactions with various signaling molecules and kinases, MYBPC participates in signal transduction pathways that regulate muscle adaptation and response to physiological stimuli.

Clinical Issues

Mutations in MYBPC genes, particularly MYBPC3, are associated with several muscle disorders:

1. Hypertrophic Cardiomyopathy (HCM): Mutations in MYBPC3 are a common cause of HCM, characterized by thickened heart walls, impaired cardiac function, and an increased risk of sudden cardiac death. HCM can be inherited in an autosomal dominant manner.
2. Dilated Cardiomyopathy (DCM): Some MYBPC3 mutations can lead to DCM, a condition marked by an enlarged and weakened heart, which impairs its ability to pump blood effectively.
3. Skeletal Muscle Disorders: While less common, mutations in MYBPC1 and MYBPC2 can lead to skeletal muscle myopathies, affecting muscle strength and function.

Summary

MYBPC proteins are integral components of the sarcomere, essential for the regulation of muscle contraction and structural integrity. The three main isoforms of MYBPC—MYBPC1, MYBPC2, and MYBPC3—are specifically expressed in slow skeletal, fast skeletal, and cardiac muscles, respectively. These proteins modulate the interactions between myosin and actin, contributing to the fine-tuning of muscle contraction. Mutations in MYBPC genes, especially MYBPC3, are implicated in serious cardiac conditions like hypertrophic and dilated cardiomyopathy. Understanding the structure, function, and pathology associated with MYBPC proteins provides critical insights into muscle physiology and the development of therapeutic strategies for related diseases.