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Straceski AJ, Geisterfer-Lowrance A, Seidman CE, et al. Functional analysis of myosin missense mutations in familial hypertrophic cardiomyopathy. Proc Natl Acad Sci U S A. 1994;91(2):589-93doi: 10.1073/pnas.91.2.589.
Straceski, A. J., Geisterfer-Lowrance, A., Seidman, C. E., Seidman, J. G., & Leinwand, L. A. (1994). Functional analysis of myosin missense mutations in familial hypertrophic cardiomyopathy. Proceedings of the National Academy of Sciences of the United States of America, 91(2), 589-93. https://doi.org/10.1073/pnas.91.2.589
Straceski, A J, et al. "Functional analysis of myosin missense mutations in familial hypertrophic cardiomyopathy." Proceedings of the National Academy of Sciences of the United States of America vol. 91,2 (1994): 589-93. doi: https://doi.org/10.1073/pnas.91.2.589
Straceski AJ, Geisterfer-Lowrance A, Seidman CE, Seidman JG, Leinwand LA. Functional analysis of myosin missense mutations in familial hypertrophic cardiomyopathy. Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):589-93. doi: 10.1073/pnas.91.2.589. PMID: 8290568; PMCID: PMC42994.
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Atypon Free PMC Article

Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):589-93. doi: 10.1073/pnas.91.2.589.

Functional analysis of myosin missense mutations in familial hypertrophic cardiomyopathy.

Proceedings of the National Academy of Sciences of the United States of America

A J Straceski, A Geisterfer-Lowrance, C E Seidman, J G Seidman, L A Leinwand

Affiliations

  1. Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.

PMID: 8290568 PMCID: PMC42994 DOI: 10.1073/pnas.91.2.589
Free PMC Article

Abstract

To analyze potential functional consequences of myosin heavy chain (MHC) mutations identified in patients with familial hypertrophic cardiomyopathy (FHC), we have assessed the stability of the mutant MHCs and their ability to form thick filaments. Constructs encoding wild-type rat alpha MHC and seven corresponding FHC missense mutants were transfected into COS cells. Immunoblot analysis suggested that FHC mutations do not grossly alter protein stability. Wild-type alpha MHC transfected into COS cells forms structures previously shown to be arrays of thick filaments, which also resemble myosin structures observed early in differentiation of muscle cells. Surprisingly, up to 29% of COS cells transfected with the FHC mutants failed to form filamentous structures. To assess whether this phenotype was specific for the FHC mutants and not generalizable to any myosin mutation, COS cells were transfected with a construct encoding an MHC with a 168-amino acid deletion of the hinge/rod region. This deletion construct formed filamentous structures with the same frequency as wild-type MHC. Biochemical analysis of one FHC mutant (Arg-249-->Gln) demonstrates that the structures formed by the mutant are solubilized at a lower ionic strength than those formed by wild-type MHC. We conclude that although the FHC mutant MHC is not labile, its assembly properties may be impaired.

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