Myosin S2 origins track evolution of strong binding on actin by azimuthal rolling of motor domain.

Journal Article (Journal Article)

Myosin crystal structures have given rise to the swinging lever arm hypothesis, which predicts a large axial tilt of the lever arm domain during the actin-attached working stroke. Previous work imaging the working stroke in actively contracting, fast-frozen Lethocerus muscle confirmed the axial tilt; but strongly bound myosin heads also showed an unexpected azimuthal slew of the lever arm around the thin filament axis, which was not predicted from known crystal structures. We hypothesized that an azimuthal reorientation of the myosin motor domain on actin during the weak-binding to strong-binding transition could explain the lever arm slew provided that myosin's α-helical coiled-coil subfragment 2 (S2) domain emerged from the thick filament backbone at a particular location. However, previous studies did not adequately resolve the S2 domain. Here we used electron tomography of rigor muscle swollen by low ionic strength to pull S2 clear of the thick filament backbone, thereby revealing the azimuth of its point of origin. The results show that the azimuth of S2 origins of those rigor myosin heads, bound to the actin target zone of actively contracting muscle, originate from a restricted region of the thick filament. This requires an azimuthal reorientation of the motor domain on actin during the weak to strong transition.

Full Text

Duke Authors

Cited Authors

  • Arakelian, C; Warrington, A; Winkler, H; Perz-Edwards, RJ; Reedy, MK; Taylor, KA

Published Date

  • March 24, 2015

Published In

Volume / Issue

  • 108 / 6

Start / End Page

  • 1495 - 1502

PubMed ID

  • 25809262

Pubmed Central ID

  • PMC4375447

Electronic International Standard Serial Number (EISSN)

  • 1542-0086

Digital Object Identifier (DOI)

  • 10.1016/j.bpj.2014.12.059


  • eng

Conference Location

  • United States