Journal article
Structural and functional aspects of the myosin essential light chain in cardiac muscle contraction
The FASEB journal, Vol.25(12), pp.4394-4405
12/2011
DOI: 10.1096/fj.11-191973
PMCID: PMC3236635
PMID: 21885653
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.—Muthu, P., Wang, L., Yuan, C.-C., Kazmierczak, K., Huang, W., Hernandez, O. M., Kawai, M., Irving, T. C., Szczesna-Cordary, D. Structural and functional aspects of the myosin essential light chain in cardiac muscle contraction.
Details
- Title: Subtitle
- Structural and functional aspects of the myosin essential light chain in cardiac muscle contraction
- Creators
- Priya Muthu - Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, Florida, USALi Wang - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa, USA; andChen-Ching Yuan - Center for Synchrotron Radiation Research and Instrumentation andKatarzyna Kazmierczak - Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, Florida, USAWenrui Huang - Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, Florida, USAOlga M Hernandez - Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, Florida, USAMasataka Kawai - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa, USA; andThomas C Irving - Center for Synchrotron Radiation Research and Instrumentation andDanuta Szczesna-Cordary - Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, Florida, USA
- Resource Type
- Journal article
- Publication Details
- The FASEB journal, Vol.25(12), pp.4394-4405
- DOI
- 10.1096/fj.11-191973
- PMID
- 21885653
- PMCID
- PMC3236635
- NLM abbreviation
- FASEB J
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Publisher
- Federation of American Societies for Experimental Biology; Bethesda, MD, USA
- Grant note
- DOI: 10.13039/100000968, name: American Heart Association, award: 10POST3420009
- Language
- English
- Date published
- 12/2011
- Academic Unit
- Anatomy and Cell Biology; Internal Medicine
- Record Identifier
- 9984025584502771
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