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Functional Characterization of Dictyostelium Discoideum Mutant Myosins Equivalent to Human Familial Hypertrophic Cardiomyopathy

  • Hideo Fujita
  • Seiryo Sugiura
  • Shin-ichi Momomura
  • Haruo Sugi
  • Kazuo Sutoh
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 453)

Abstract

Familial hypertrophic cardiomyopathy(FHC) is caused by missence mutations in β-myosin heavy chain or other various sarcomeric proteins. To elucidate the functional impact of FHC mutations in myosin heavy chain, we generated Dictyostelium discoideum myosin II mutants equivalent to human FHC mutations by site-directed mutagenesis, and characterized their molecular-basis motor function. The current mutants, i.e. R397Q, F506C, G575R, A699R, K703Q and K703W are equivalent to R403Q, F513C, G584R, G716R, R719Q and R719W FHC mutants respectively. We measured the molecular-basis force and the sliding velocity generated by these myosin mutants. The measurement revealed that the A699R, K703Q and K703W myosins exhibited the lowest level of force with their preserved actin-activated MgATPase activity. F506C mutant showed the least impairment of the motile and enzymatic activities. The motor function of R397Q and G575R myosins were classified as intermediate. These results suggest that ELC binding domain might be important for force production.

Keywords

Actin Filament Myosin Heavy Chain Motor Domain Sarcomeric Protein Myosin Motor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1998

Authors and Affiliations

  • Hideo Fujita
    • 1
  • Seiryo Sugiura
    • 1
  • Shin-ichi Momomura
    • 1
  • Haruo Sugi
    • 2
  • Kazuo Sutoh
    • 3
  1. 1.Second Department of Internal MedicineUniversity of TokyoHongo, Tokyo 113Japan
  2. 2.Department of Physiology, School of MedicineTeikyo UniversityKaga, Tokyo 173Japan
  3. 3.Department of Life Sciences, Graduate School of Arts and SciencesUniversity of TokyoKomaba, Tokyo 153Japan

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