|2k1m, 20 NMR models ()|
|Gene:||MYBPC3 (Homo sapiens)|
3D NMR structure of domain cC0 of cardiac myosin binding protein C (MyBPC)
Myosin-binding protein C (MyBP-C) is a multidomain protein present in the thick filaments of striated muscles and is involved in both sarcomere formation and contraction regulation. The latter function is believed to be located at the N terminus, which is close to the motor domain of myosin. The cardiac isoform of MyBP-C is linked to hypertrophic cardiomyopathy. Here, we use NMR spectroscopy and biophysical and biochemical assays to study the three-dimensional structure and interactions of the cardiac-specific Ig-like domain C0, a part of cardiac MyBP-C of which little is known. The structure confirmed that C0 is a member of the IgI class of proteins, showing many of the characteristic features of this fold. Moreover, we identify a novel interaction between C0 and the regulatory light chain of myosin, thus placing the N terminus of the protein in proximity to the motor domain of myosin. This novel interaction is disrupted by several cardiomyopathy-linked mutations in the MYBPC3 gene. These results provide new insights into how cardiac MyBP-C incorporates in the sarcomere and how it can contribute to the regulation of muscle contraction.
Structure and interactions of myosin-binding protein C domain C0: cardiac-specific regulation of myosin at its neck?, Ratti J, Rostkova E, Gautel M, Pfuhl M, J Biol Chem. 2011 Apr 8;286(14):12650-8. Epub 2011 Feb 5. PMID:021297165
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
[MYPC3_HUMAN] Defects in MYBPC3 are the cause of familial hypertrophic cardiomyopathy type 4 (CMH4) [MIM:115197]. Familial hypertrophic cardiomyopathy is a hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.
[MYPC3_HUMAN] Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. In vitro it binds MHC, F-actin and native thin filaments, and modifies the activity of actin-activated myosin ATPase. It may modulate muscle contraction or may play a more structural role.
About this Structure
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