title: The myosin converter domain modulates muscle performance.
abstract: Myosin is the molecular motor that powers muscle contraction as a result of conformational changes during its mechanochemical cycle. We demonstrate that the converter, a compact structural domain that differs in sequence between Drosophila melanogaster myosin isoforms, dramatically influences the kinetic properties of myosin and muscle fibres. Transgenic replacement of the converter in the fast indirect flight muscle with the converter from an embryonic muscle slowed muscle kinetics, forcing a compensatory reduction in wing beat frequency to sustain flight. Conversely, replacing the embryonic converter with the flight muscle converter sped up muscle kinetics and increased maximum power twofold, compared to flight muscles expressing the embryonic myosin isoform. The substitutions also dramatically influenced in vitro actin sliding velocity, suggesting that the converter modulates a rate-limiting step preceding cross-bridge detachment. Our integrative analysis demonstrates that isoform-specific differences in the myosin converter allow different muscle types to meet their specific locomotion demands.
authors.affiliation: Department of Biology, Molecular Biology Institute, and the Heart Institute, San Diego State University, San Diego, California 92182-4614, USA. dswank@sciences.sdsu.edu
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Swank
authors.forename: Aileen F
authors.initials: AF
authors.lastname: Knowles
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Suggs
authors.forename: Floyd
authors.initials: F
authors.lastname: Sarsoza
authors.forename: Annie
authors.initials: A
authors.lastname: Lee
authors.forename: David W
authors.initials: DW
authors.lastname: Maughan
authors.forename: Sanford I
authors.initials: SI
authors.lastname: Bernstein
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D002645:Chickens; D018076:DNA, Complementary / Q000378:metabolism; D004331:Drosophila melanogaster; D007700:Kinetics; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000648:ultrastructure; D009132:Muscles / Q000166:cytology*; D015879:Myosin Subfragments / Q000737:chemistry; D009218:Myosins / Q000737:chemistry* / Q000378:metabolism; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013696:Temperature; D019076:Transgenes
chemical_list: D018076:DNA, Complementary; D015879:Myosin Subfragments; D020033:Protein Isoforms; D009218:Myosins