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Distinct sequences and post-translational modifications in cardiac atrial and ventricular myosin light chains revealed by top-down mass spectrometry
- Source :
- Journal of Molecular and Cellular Cardiology. 107:13-21
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Myosin is the principal component of the thick filaments that, through interactions with the actin thin filaments, mediates force production during muscle contraction. Myosin is a hexamer, consisting of two heavy chains, each associated with an essential (ELC) and a regulatory (RLC) light chain, which bind the lever-arm of the heavy chain and play important modulatory roles in striated muscle contraction. Nevertheless, a comprehensive assessment of the sequences of the ELC and RLC isoforms, as well as their post-translational modifications, in the heart remains lacking. Herein, utilizing top-down high-resolution mass spectrometry (MS), we have comprehensively characterized the sequences and N-terminal modifications of the atrial and ventricular isoforms of the myosin light chains from human and swine hearts, as well as the sites of phosphorylation in the swine proteins. In addition to the correction of disparities in the database sequences of the swine proteins, we show for the first time that, whereas the ventricular isoforms of the ELC and RLC are methylated at their N-termini, which is consistent with previous studies, the atrial isoforms of the ELC and RLC from both human and swine are Nα-methylated and Nα-acetylated, respectively. Furthermore, top-down MS with electron capture dissociation enabled localization of the sites of phosphorylation in swine RLC isoforms from the ventricles and atria to Ser14 and Ser22, respectively. Collectively, these results provide new insights into the sequences and modifications of myosin light chain isoforms in the human and swine hearts, which will pave the way for a better understanding of their functional roles in cardiac physiology and pathophysiology.
- Subjects :
- Sarcomeres
0301 basic medicine
Gene isoform
Myosin Light Chains
Myosin light-chain kinase
Swine
Heart Ventricles
macromolecular substances
Immunoglobulin light chain
Article
03 medical and health sciences
Myosin
medicine
Animals
Humans
Protein Isoforms
Heart Atria
Phosphorylation
Molecular Biology
Actin
030102 biochemistry & molecular biology
Chemistry
Myocardium
Striated muscle contraction
Cell biology
030104 developmental biology
Biochemistry
medicine.symptom
Cardiology and Cardiovascular Medicine
Protein Processing, Post-Translational
Muscle contraction
Subjects
Details
- ISSN :
- 00222828
- Volume :
- 107
- Database :
- OpenAIRE
- Journal :
- Journal of Molecular and Cellular Cardiology
- Accession number :
- edsair.doi.dedup.....d236366488bef96a07ee58c247409497