title: Structural and functional aspects of the myosin essential light chain in cardiac muscle contraction.
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.
authors: Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, 1600 NW 10th Ave., Miami, FL 33136, USA.
authors: Priya
authors: P
authors: Muthu
authors: Li
authors: L
authors: Wang
authors: Chen-Ching
authors: CC
authors: Yuan
authors: Katarzyna
authors: K
authors: Kazmierczak
authors: Wenrui
authors: W
authors: Huang
authors: Olga M
authors: OM
authors: Hernandez
authors: Masataka
authors: M
authors: Kawai
authors: Thomas C
authors: TC
authors: Irving
authors: Danuta
authors: D
authors: Szczesna-Cordary
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D009200:Myocardial Contraction / Q000235:genetics / Q000502:physiology*; D009206:Myocardium / Q000473:pathology; D018994:Myosin Light Chains / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D010210:Papillary Muscles / Q000473:pathology / Q000503:physiopathology; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014961:X-Ray Diffraction
chemical_list: D050505:Mutant Proteins; D018994:Myosin Light Chains; D010446:Peptide Fragments; D011994:Recombinant Proteins