Myosin VI undergoes a 180° power stroke implying an uncoupling of the front lever arm

Jeff G. Reifenberger, Erdal Toprak, HyeongJun Kim, Dan Safer, H. Lee Sweeney, Paul R. Selvin

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

We simultaneously measure both the step size, via FIONA, and the 3-D orientation, via DOPI, of the light-chain domain of individual dimeric myosin VIs. This allows for the correlation of the change in orientation of the light chain domain to the stepping of the motor. Three different pairs of positions were tested using a rigid bifunctional rhodamine on the calmodulin of the IQ domain. The data for all three labeling positions support the model that the light chain domain undergoes a significant rotation of approximately 180°. Contrary to an earlier study [Sun, Y. et al. (2007) Mol Cell 28, 954-964], our data does not support a model of multiple angles of the lever arm of the lead head, nor "wiggly" walking on actin. Instead, we propose that for the two heads of myosin VI to coordinate their processive movement, the lever arm of the lead head must be uncoupled from the converter until the rear head detaches. More specifically, intramolecular strain causes the myosin VI lever arm of the lead head to uncouple from the motor domain, allowing the motor domain to go through its product-release (phosphate and ADP) steps at an unstrained rate. The lever arm of the lead head rebinds to the motor and attains a rigor conformationwhen the rear head detaches. By coupling the orientation and position information with previously described kinetics, this allows us to explain how myosin VI coordinates its heads processively while maintaining the ability to move under load with a (semi-) rigid lever arm.

Original languageEnglish (US)
Pages (from-to)18255-18260
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number43
DOIs
StatePublished - 2009

Keywords

  • FIONA
  • Fluorescence
  • Motility
  • Single molecule assay
  • Unconventional myosin

ASJC Scopus subject areas

  • General

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