Structural and functional aspects of the myosin essential light chain in cardiac muscle contraction

Priya Muthu, Li Wang, Chen Ching Yuan, Katarzyna Kazmierczak, Wenrui Huang, Olga M. Hernandez, Masataka Kawai, Thomas C. Irving, Danuta Szczesna-Cordary

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

The myosin essential light chain (ELC) is a structural component of the actomyosin cross-bridge, but its function is poorly understood, especially the role of the cardiac specific N-terminal extension in modulating actomyosin interaction. Here, we generated transgenic (Tg) mice expressing the A57G (alanine to glycine) mutation in the cardiac ELC known to cause familial hypertrophic cardiomyopathy (FHC). The function of the ELC N-terminal extension was investigated with the Tg-Δ43 mouse model, whose myocardium expresses a truncated ELC. Low-angle X-ray diffraction studies on papillary muscle fibers in rigor revealed a decreased interfilament spacing (∼1.5 nm) and no alterations in cross-bridge mass distribution in Tg-A57G mice compared to Tg-WT, expressing the full-length nonmutated ELC. The truncation mutation showed a 1.3-fold increase in I 1,1/I 1,0, indicating a shift of cross-bridge mass from the thick filament backbone toward the thin filaments. Mechanical studies demonstrated increased stiffness in Tg-A57G muscle fibers compared to Tg-WT or Tg-Δ43. The equilibrium constant for the cross-bridge force generation step was smallest in Tg-Δ43. These results support an important role for the N-terminal ELC extension in prepositioning the cross-bridge for optimal force production. Subtle changes in the ELC sequence were sufficient to alter cross-bridge properties and lead to pathological phenotypes.

Original languageEnglish (US)
Pages (from-to)4394-4405
Number of pages12
JournalFASEB Journal
Volume25
Issue number12
DOIs
StatePublished - Dec 1 2011

Keywords

  • Cross-bridge kinetics
  • FHC-linked ELC mutation
  • Myofilament lattice spacing
  • Transgenic mice

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

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  • Cite this

    Muthu, P., Wang, L., Yuan, C. C., Kazmierczak, K., Huang, W., Hernandez, O. M., Kawai, M., Irving, T. C., & Szczesna-Cordary, D. (2011). Structural and functional aspects of the myosin essential light chain in cardiac muscle contraction. FASEB Journal, 25(12), 4394-4405. https://doi.org/10.1096/fj.11-191973