Analysis of myosin heavy chain functionality in the heart - PubMed (original) (raw)

. 2003 May 9;278(19):17466-74.

doi: 10.1074/jbc.M210804200. Epub 2003 Mar 6.

Atsushi Sanbe, Florence Bouyer-Dalloz, James Gulick, Raisa Klevitsky, Timothy E Hewett, Hanna E Osinska, John N Lorenz, Christine Brosseau, Andrea Federico, Norman R Alpert, David M Warshaw, M Benjamin Perryman, Steve M Helmke, Jeffrey Robbins

Affiliations

Free article

Analysis of myosin heavy chain functionality in the heart

Maike Krenz et al. J Biol Chem. 2003.

Free article

Abstract

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.

PubMed Disclaimer

Similar articles

Cited by

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources