Our aim was to investigate the potential functional consequences of myosin heavy chain (MHC) mutations identified in patients with familial hypertrophic cardiomyopathy. We observed the presence of a mutated beta-MHC mRNA in a formalin-fixed paraffin-embedded myocardial tissue of a proband from family A, which Geisterfer-Lowrance et al. [Geisterfer-Lowrance, Kass, Tanigawa, Vosberg, McKenna, Seidman and Seidman (1990) Cell 62, 999-1006] identified as carrying the Arg-403 to Gln mutation. Recombinant DNA methods were then used to obtain size-limited, soluble and undenatured fragments of mutated myosin subfragment 1 focused around the 403 mutation. The present analysis indicated that the 403 mutation did not quantitatively alter the actin- or ATP-binding capacities of two 246-residue or 524-residue-long recombinant MHC fragments containing this mutation. The absence of any apparent impact of the 403 mutation in the recombinant MHC fragments on interactions between actin and ATP is discussed in relation to numerous biochemical and structural reports which demonstrate the crucial role of the central MHC segment, where the 403 mutation occurs, in myosin functions.
The cardiac myosin heavy chain Arg-403→Gln mutation that causes hypertrophic cardiomyopathy does not affect the actin- or ATP-binding capacities of two size-limited recombinant myosin heavy chain fragments
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P Eldin, M Le Cunff, D Mornet, J J Léger; The cardiac myosin heavy chain Arg-403→Gln mutation that causes hypertrophic cardiomyopathy does not affect the actin- or ATP-binding capacities of two size-limited recombinant myosin heavy chain fragments. Biochem J 1 March 1995; 306 (2): 345–351. doi: https://doi.org/10.1042/bj3060345
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