Analysis of Myosin Heavy Chain Functionality in the Heart
| Autor: | Jeffrey Robbins, Christine Brosseau, Norman R. Alpert, Hanna Osinska, John N. Lorenz, Andrea Federico, David M. Warshaw, Raisa Klevitsky, M. Benjamin Perryman, Maike Krenz, Florence Bouyer-Dalloz, Steve M. Helmke, James Gulick, Timothy E. Hewett, Atsushi Sanbe |
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| Rok vydání: | 2003 |
| Předmět: |
Gene isoform
Myosin light-chain kinase Recombinant Fusion Proteins ATPase Molecular Sequence Data Mice Transgenic Calcium-Transporting ATPases macromolecular substances Biochemistry Protein filament Mice Myosin head Cardiac Myosins Myosin Animals Protein Isoforms Amino Acid Sequence Molecular Biology Myosin Heavy Chains biology Myocardium Heart Cell Biology Cell biology biology.protein Calcium MYH7 |
| Zdroj: | Journal of Biological Chemistry. 278:17466-17474 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m210804200 |
| Popis: | Comparison of mammalian cardiac alpha- and beta-myosin heavy chain isoforms reveals 93% identity. To date, genetic methodologies have effected only minor switches in the mammalian cardiac myosin isoforms. Using cardiac-specific transgenesis, we have now obtained major myosin isoform shifts and/or replacements. Clusters of non-identical amino acids are found in functionally important regions, i.e. the surface loops 1 and 2, suggesting that these structures may regulate isoform-specific characteristics. Loop 1 alters filament sliding velocity, whereas Loop 2 modulates actin-activated ATPase rate in Dictyostelium myosin, but this remains untested in mammalian cardiac myosins. Alpha --beta isoform switches were engineered into mouse hearts via transgenesis. To assess the structural basis of isoform diversity, chimeric myosins in which the sequences of either Loop 1+Loop 2 or Loop 2 of alpha-myosin were exchanged for those of beta-myosin were expressed in vivo. 2-fold differences in filament sliding velocity and ATPase activity were found between the two isoforms. Filament sliding velocity of the Loop 1+Loop 2 chimera and the ATPase activities of both loop chimeras were not significantly different compared with alpha-myosin. In mouse cardiac isoforms, myosin functionality does not depend on Loop 1 or Loop 2 sequences and must lie partially in other non-homologous residues. |
| Databáze: | OpenAIRE |
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