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Titolo:
Mutations in beta-myosin S2 that cause familial hypertrophic cardiomyopathy (FHC) abolish the interaction with the regulatory domain of myosin-binding protein-C
Autore:
Gruen, M; Gautel, M;
Indirizzi:
Max Planck Inst Mol Physiol, D-44139 Dortmund, Germany Max Planck Inst MolPhysiol Dortmund Germany D-44139 9 Dortmund, Germany European Mol Biol Lab, D-69012 Heidelberg, Germany European Mol Biol Lab Heidelberg Germany D-69012 012 Heidelberg, Germany
Titolo Testata:
JOURNAL OF MOLECULAR BIOLOGY
fascicolo: 3, volume: 286, anno: 1999,
pagine: 933 - 949
SICI:
0022-2836(19990226)286:3<933:MIBSTC>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
CHICKEN SKELETAL-MUSCLE; HEAD-TAIL JUNCTION; CARDIAC MYOSIN; MYOFIBRILLAR PROTEIN; MYOGENIC CELLS; SITE MUTATION; MYBP-C; PHOSPHORYLATION; GENE; TITIN;
Keywords:
myosin; myosin-binding protein-C; coiled-coil; hypertrophic cardiomyopathy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
70
Recensione:
Indirizzi per estratti:
Indirizzo: Gautel, M Max Planck Inst Mol Physiol, Rheinlanddamm 201, D-44139 Dortmund, Germany Max Planck Inst Mol Physiol Rheinlanddamm 201 Dortmund Germany D-44139
Citazione:
M. Gruen e M. Gautel, "Mutations in beta-myosin S2 that cause familial hypertrophic cardiomyopathy (FHC) abolish the interaction with the regulatory domain of myosin-binding protein-C", J MOL BIOL, 286(3), 1999, pp. 933-949

Abstract

The 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 isolatedmyofibrils, 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 (K-d approximate to 60 mu M for R870H compared with a K-d of approximate to 5 mu M 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. (C) 1999 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/12/20 alle ore 16:10:13