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 Citations (Scopus)

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

Fingerprint

Myosin Light Chains
Muscle Contraction
Muscle
Myocardium
Light
Transgenic Mice
Actomyosin
Familial Hypertrophic Cardiomyopathy
Mutation
Papillary Muscles
Fibers
Equilibrium constants
X-Ray Diffraction
Alanine
Glycine
Stiffness
Phenotype
X ray diffraction
Muscles

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Structural and functional aspects of the myosin essential light chain in cardiac muscle contraction. / Muthu, Priya; Wang, Li; Yuan, Chen Ching; Kazmierczak, Katarzyna; Huang, Wenrui; Hernandez, Olga M.; Kawai, Masataka; Irving, Thomas C.; Szczesna-Cordary, Danuta.

In: FASEB Journal, Vol. 25, No. 12, 01.12.2011, p. 4394-4405.

Research output: Contribution to journalArticle

Muthu, P, Wang, L, Yuan, CC, Kazmierczak, K, Huang, W, Hernandez, OM, Kawai, M, Irving, TC & Szczesna-Cordary, D 2011, 'Structural and functional aspects of the myosin essential light chain in cardiac muscle contraction', FASEB Journal, vol. 25, no. 12, pp. 4394-4405. https://doi.org/10.1096/fj.11-191973
Muthu P, Wang L, Yuan CC, Kazmierczak K, Huang W, Hernandez OM et al. Structural and functional aspects of the myosin essential light chain in cardiac muscle contraction. FASEB Journal. 2011 Dec 1;25(12):4394-4405. https://doi.org/10.1096/fj.11-191973
Muthu, Priya ; Wang, Li ; Yuan, Chen Ching ; Kazmierczak, Katarzyna ; Huang, Wenrui ; Hernandez, Olga M. ; Kawai, Masataka ; Irving, Thomas C. ; Szczesna-Cordary, Danuta. / Structural and functional aspects of the myosin essential light chain in cardiac muscle contraction. In: FASEB Journal. 2011 ; Vol. 25, No. 12. pp. 4394-4405.
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