PubMed:10024460 JSONTXT

{"project":"DisGeNET5_gene_disease","denotations":[{"id":"10024460-0#151#160#gene5554","span":{"begin":151,"end":160},"obj":"gene5554"},{"id":"10024460-0#151#160#gene5555","span":{"begin":151,"end":160},"obj":"gene5555"},{"id":"10024460-0#151#160#gene5554","span":{"begin":151,"end":160},"obj":"gene5554"},{"id":"10024460-0#151#160#gene5555","span":{"begin":151,"end":160},"obj":"gene5555"},{"id":"10024460-0#39#75#diseaseC0949658","span":{"begin":39,"end":75},"obj":"diseaseC0949658"},{"id":"10024460-0#77#80#diseaseC0745103","span":{"begin":77,"end":80},"obj":"diseaseC0745103"}],"relations":[{"id":"151#160#gene555439#75#diseaseC0949658","pred":"associated_with","subj":"10024460-0#151#160#gene5554","obj":"10024460-0#39#75#diseaseC0949658"},{"id":"151#160#gene555477#80#diseaseC0745103","pred":"associated_with","subj":"10024460-0#151#160#gene5554","obj":"10024460-0#77#80#diseaseC0745103"},{"id":"151#160#gene555539#75#diseaseC0949658","pred":"associated_with","subj":"10024460-0#151#160#gene5555","obj":"10024460-0#39#75#diseaseC0949658"},{"id":"151#160#gene555577#80#diseaseC0745103","pred":"associated_with","subj":"10024460-0#151#160#gene5555","obj":"10024460-0#77#80#diseaseC0745103"},{"id":"151#160#gene555439#75#diseaseC0949658","pred":"associated_with","subj":"10024460-0#151#160#gene5554","obj":"10024460-0#39#75#diseaseC0949658"},{"id":"151#160#gene555477#80#diseaseC0745103","pred":"associated_with","subj":"10024460-0#151#160#gene5554","obj":"10024460-0#77#80#diseaseC0745103"},{"id":"151#160#gene555539#75#diseaseC0949658","pred":"associated_with","subj":"10024460-0#151#160#gene5555","obj":"10024460-0#39#75#diseaseC0949658"},{"id":"151#160#gene555577#80#diseaseC0745103","pred":"associated_with","subj":"10024460-0#151#160#gene5555","obj":"10024460-0#77#80#diseaseC0745103"}],"text":"Mutations in beta-myosin S2 that cause familial hypertrophic cardiomyopathy (FHC) abolish the interaction with the regulatory domain of myosin-binding protein-C.\nThe myosin filaments of striated muscle contain a family of enigmatic myosin-binding proteins (MyBP), MyBP-C and MyBP-H. These modular proteins of the intracellular immunoglobulin superfamily contain unique domains near their N termini. The N-terminal domain of cardiac MyBP-C, the MyBP-C motif, contains additional phosphorylation sites and may regulate contraction in a phosphorylation dependent way. In contrast to the C terminus, which binds to the light meromyosin portion of the myosin rod, the interactions of this domain are unknown. We demonstrate that fragments of MyBP-C containing the MyBP-C motif localise to the sarcomeric A-band in cardiomyocytes and isolated myofibrils, without affecting sarcomere structure. The binding site for the MyBP-C motif resides in the N-terminal 126 residues of the S2 segment of the myosin rod. In this region, several mutations in beta-myosin are associated with FHC; however, their molecular implications remained unclear. We show that two representative FHC mutations in beta-myosin S2, R870H and E924K, drastically reduce MyBP-C binding (Kd approximately 60 microM for R870H compared with a Kd of approximately 5 microM for the wild-type) down to undetectable levels (E924K). These mutations do not affect the coiled-coil structure of myosin. We suggest that the regulatory function of MyBP-C is mediated by the interaction with S2, and that mutations in beta-myosin S2 may act by altering the interactions with MyBP-C."}

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in beta-myosin S2 that cause familial hypertrophic cardiomyopathy (FHC) abolish the interaction with the regulatory domain of myosin-binding protein-C.\nThe myosin filaments of striated muscle contain a family of enigmatic myosin-binding proteins (MyBP), MyBP-C and MyBP-H. These modular proteins of the intracellular immunoglobulin superfamily contain unique domains near their N termini. The N-terminal domain of cardiac MyBP-C, the MyBP-C motif, contains additional phosphorylation sites and may regulate contraction in a phosphorylation dependent way. In contrast to the C terminus, which binds to the light meromyosin portion of the myosin rod, the interactions of this domain are unknown. We demonstrate that fragments of MyBP-C containing the MyBP-C motif localise to the sarcomeric A-band in cardiomyocytes and isolated myofibrils, without affecting sarcomere structure. The binding site for the MyBP-C motif resides in the N-terminal 126 residues of the S2 segment of the myosin rod. In this region, several mutations in beta-myosin are associated with FHC; however, their molecular implications remained unclear. We show that two representative FHC mutations in beta-myosin S2, R870H and E924K, drastically reduce MyBP-C binding (Kd approximately 60 microM for R870H compared with a Kd of approximately 5 microM for the wild-type) down to undetectable levels (E924K). These mutations do not affect the coiled-coil structure of myosin. We suggest that the regulatory function of MyBP-C is mediated by the interaction with S2, and that mutations in beta-myosin S2 may act by altering the interactions with MyBP-C."}

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":517,"end":528},"obj":"HP_0001371"}],"text":"Mutations in beta-myosin S2 that cause familial hypertrophic cardiomyopathy (FHC) abolish the interaction with the regulatory domain of myosin-binding protein-C.\nThe myosin filaments of striated muscle contain a family of enigmatic myosin-binding proteins (MyBP), MyBP-C and MyBP-H. These modular proteins of the intracellular immunoglobulin superfamily contain unique domains near their N termini. The N-terminal domain of cardiac MyBP-C, the MyBP-C motif, contains additional phosphorylation sites and may regulate contraction in a phosphorylation dependent way. In contrast to the C terminus, which binds to the light meromyosin portion of the myosin rod, the interactions of this domain are unknown. We demonstrate that fragments of MyBP-C containing the MyBP-C motif localise to the sarcomeric A-band in cardiomyocytes and isolated myofibrils, without affecting sarcomere structure. The binding site for the MyBP-C motif resides in the N-terminal 126 residues of the S2 segment of the myosin rod. In this region, several mutations in beta-myosin are associated with FHC; however, their molecular implications remained unclear. We show that two representative FHC mutations in beta-myosin S2, R870H and E924K, drastically reduce MyBP-C binding (Kd approximately 60 microM for R870H compared with a Kd of approximately 5 microM for the wild-type) down to undetectable levels (E924K). These mutations do not affect the coiled-coil structure of myosin. We suggest that the regulatory function of MyBP-C is mediated by the interaction with S2, and that mutations in beta-myosin S2 may act by altering the interactions with MyBP-C."}

{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":151,"end":160},"obj":"gene:5555"},{"id":"T1","span":{"begin":39,"end":75},"obj":"disease:C0949658"},{"id":"T2","span":{"begin":151,"end":160},"obj":"gene:5554"},{"id":"T3","span":{"begin":39,"end":75},"obj":"disease:C0949658"},{"id":"T4","span":{"begin":151,"end":160},"obj":"gene:5555"},{"id":"T5","span":{"begin":77,"end":80},"obj":"disease:C0745103"},{"id":"T6","span":{"begin":151,"end":160},"obj":"gene:5554"},{"id":"T7","span":{"begin":77,"end":80},"obj":"disease:C0745103"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"},{"id":"R3","pred":"associated_with","subj":"T4","obj":"T5"},{"id":"R4","pred":"associated_with","subj":"T6","obj":"T7"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"Mutations in beta-myosin S2 that cause familial hypertrophic cardiomyopathy (FHC) abolish the interaction with the regulatory domain of myosin-binding protein-C.\nThe myosin filaments of striated muscle contain a family of enigmatic myosin-binding proteins (MyBP), MyBP-C and MyBP-H. These modular proteins of the intracellular immunoglobulin superfamily contain unique domains near their N termini. The N-terminal domain of cardiac MyBP-C, the MyBP-C motif, contains additional phosphorylation sites and may regulate contraction in a phosphorylation dependent way. In contrast to the C terminus, which binds to the light meromyosin portion of the myosin rod, the interactions of this domain are unknown. We demonstrate that fragments of MyBP-C containing the MyBP-C motif localise to the sarcomeric A-band in cardiomyocytes and isolated myofibrils, without affecting sarcomere structure. The binding site for the MyBP-C motif resides in the N-terminal 126 residues of the S2 segment of the myosin rod. In this region, several mutations in beta-myosin are associated with FHC; however, their molecular implications remained unclear. We show that two representative FHC mutations in beta-myosin S2, R870H and E924K, drastically reduce MyBP-C binding (Kd approximately 60 microM for R870H compared with a Kd of approximately 5 microM for the wild-type) down to undetectable levels (E924K). These mutations do not affect the coiled-coil structure of myosin. We suggest that the regulatory function of MyBP-C is mediated by the interaction with S2, and that mutations in beta-myosin S2 may act by altering the interactions with MyBP-C."}