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Cardiac myosin binding protein C
1Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6085, USA. bsg@mail.med.upenn.edu
Insights
Myosin binding protein C (MyBP-C) is crucial for muscle structure and function. It aids in sarcomere formation and, in cardiac muscle, regulates contraction through phosphorylation.
Area of Science:
- Muscle physiology
- Molecular biology
- Biochemistry
Background:
- Myosin binding protein C (MyBP-C) is a key component of myofibrils in striated muscle.
- It is located in the C zone of the A band, interacting with myosin and titin.
- Three isoforms exist: slow skeletal, fast skeletal, and cardiac.
Purpose of the Study:
- To elucidate the dual functions of MyBP-C in muscle.
- To investigate its role in sarcomeric myofibril formation.
- To explore its function in regulating cardiac contraction via phosphorylation.
Main Methods:
- Analysis of MyBP-C's binding interactions with myosin and titin.
- Observation of MyBP-C's role during myofibrillogenesis.
- Investigation of cardiac MyBP-C phosphorylation sites and their effects.
Main Results:
- MyBP-C binding to myosin and titin is essential for proper sarcomere formation.
- Cardiac MyBP-C possesses unique phosphorylation sites and an N-terminal immunoglobulin module.
- Phosphorylation of cardiac MyBP-C influences thick filament structure and cardiac contractility.
Conclusions:
- MyBP-C is vital for the structural integrity of sarcomeres through myosin and titin binding.
- Cardiac MyBP-C phosphorylation serves as a regulatory mechanism for heart contraction.
- MyBP-C plays a significant role in both muscle structure and cardiac function modulation.
Abstract:
Myosin binding protein C (MyBP-C) is one of a group of myosin binding proteins that are present in the myofibrils of all striated muscle. The protein is found at 43-nm repeats along 7 to 9 transverse lines in a portion of the A band where crossbridges are found (C zone). MyBP-C contains myosin and titin binding sites at the C terminus of the molecule in all 3 of the isoforms (slow skeletal, fast skeletal, and cardiac). The cardiac isoform also includes a series of residues that contain 3 phosphorylatable sites and an additional immunoglobulin module at the N terminus that are not present in skeletal isoforms. The following 2 major functions of MyBP-C have been suggested: (1) a role in the formation of the sarcomeric myofibril as a result of binding to myosin and titin and (2) in the case of the cardiac isoform, regulation of contraction through phosphorylation. The first is supported by the demonstrated effect of MyBP-C on the packing of myosin in the thick filament, the coincidence of appearance of sarcomeres and MyBP-C during myofibrillogenesis, and the defective formation of sarcomeres when the titin and/or myosin binding sites of MyBP-C are missing. The second is supported by the specific phosphorylation sites in cardiac MyBP-C, the presence in the thick filament of an enzyme specific for MyBP-C phosphorylation, the alteration of thick filament structure by MyBP-C phosphorylation, and the accompaniment of MyBP-C phosphorylation with all major physiological mechanisms of modulation of inotropy in the heart.