Alternative S2 hinge regions of the myosin rod affect myofibrillar structure and myosin kinetics

Biophys J. 2009 May 20;96(10):4132-43. doi: 10.1016/j.bpj.2009.02.034.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Biomechanical Phenomena
  • Drosophila Proteins / chemistry*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Drosophila melanogaster / physiology
  • Flight, Animal / physiology
  • Humans
  • Kinetics
  • Microscopy, Electron
  • Molecular Sequence Data
  • Muscle Fibers, Skeletal / physiology
  • Myofibrils / chemistry*
  • Myofibrils / physiology
  • Myosin Subfragments / chemistry
  • Myosin Subfragments / genetics*
  • Myosin Subfragments / metabolism*
  • Myosin Type II / chemistry*
  • Myosin Type II / genetics
  • Myosin Type II / metabolism*
  • Sarcomeres / chemistry
  • Sarcomeres / physiology
  • X-Ray Diffraction

Substances

  • Drosophila Proteins
  • Myosin Subfragments
  • Adenosine Triphosphatases
  • Myosin Type II