title: Alternative S2 hinge regions of the myosin rod affect myofibrillar structure and myosin kinetics.
abstract: The subfragment 2/light meromyosin "hinge" region has been proposed to significantly contribute to muscle contraction force and/or speed. Transgenic replacement of the endogenous fast muscle isovariant hinge A (exon 15a) in Drosophila melanogaster indirect flight muscle with the slow muscle hinge B (exon 15b) allows examination of the structural and functional changes when only this region of the myosin molecule is different. Hinge B was previously shown to increase myosin rod length, increase A-band and sarcomere length, and decrease flight performance compared to hinge A. We applied additional measures to these transgenic lines to further evaluate the consequences of modifying this hinge region. Structurally, the longer A-band and sarcomere lengths found in the hinge B myofibrils appear to be due to the longitudinal addition of myosin heads. Functionally, hinge B, although a significant distance from the myosin catalytic domain, alters myosin kinetics in a manner consistent with this region increasing myosin rod length. These structural and functional changes combine to decrease whole fly wing-beat frequency and flight performance. Our results indicate that this hinge region plays an important role in determining myosin kinetics and in regulating thick and thin filament lengths as well as sarcomere length.
authors.affiliation: Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, Vermont, USA. Mark.Miller@uvm.edu
authors.forename: Mark S
authors.initials: MS
authors.lastname: Miller
authors.forename: Corey M
authors.initials: CM
authors.lastname: Dambacher
authors.forename: Aileen F
authors.initials: AF
authors.lastname: Knowles
authors.forename: Joan M
authors.initials: JM
authors.lastname: Braddock
authors.forename: Gerrie P
authors.initials: GP
authors.lastname: Farman
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Irving
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Swank
authors.forename: Sanford I
authors.initials: SI
authors.lastname: Bernstein
authors.forename: David W
authors.initials: DW
authors.lastname: Maughan
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001696:Biomechanical Phenomena; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D005426:Flight, Animal / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D009210:Myofibrils / Q000737:chemistry* / Q000502:physiology; D015879:Myosin Subfragments / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D024462:Myosin Type II / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012518:Sarcomeres / Q000737:chemistry / Q000502:physiology; D014961:X-Ray Diffraction
chemical_list: D029721:Drosophila Proteins; D015879:Myosin Subfragments; D000251:Adenosine Triphosphatases; D024462:Myosin Type II