Load-dependent ADP binding to myosins V and VI

Implications for subunit coordination and function

Yusuke Oguchi, Sergey Mikhailenko, Takashi Ohki, Adrian O. Olivares, Enrique M. De La Cruz, Shin'ichi Ishiwata

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Dimeric myosins V and VI travel long distances in opposite directions along actin filaments in cells, taking multiple steps in a "hand-over-hand" fashion. The catalytic cycles of both myosins are limited by ADP dissociation, which is considered a key step in the walking mechanism of these motors. Here, we demonstrate that external loads applied to individual actomyosin V or VI bonds asymmetrically affect ADP affinity, such that ADP binds weaker under loads assisting motility. Model-based analysis reveals that forward and backward loads modulate the kinetics of ADP binding to both myosins, although the effect is less pronounced for myosin VI. ADP dissociation is modestly accelerated by forward loads and inhibited by backward loads. Loads applied in either direction slow ADP binding to myosin V but accelerate binding to myosin VI. We calculate that the intramolecular load generated during processive stepping is ≈2 pN for both myosin V and myosin VI. The distinct load dependence of ADP binding allows these motors to perform different cellular functions.

Original languageEnglish
Pages (from-to)7714-7719
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number22
DOIs
Publication statusPublished - 2008 Jun 3

Fingerprint

Myosin Type V
Adenosine Diphosphate
Myosins
Hand
Actomyosin
myosin VI
Actin Cytoskeleton
Walking

Keywords

  • Gating mechanism
  • Intramolecular load
  • Molecular motors
  • Processivity

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Load-dependent ADP binding to myosins V and VI : Implications for subunit coordination and function. / Oguchi, Yusuke; Mikhailenko, Sergey; Ohki, Takashi; Olivares, Adrian O.; De La Cruz, Enrique M.; Ishiwata, Shin'ichi.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 22, 03.06.2008, p. 7714-7719.

Research output: Contribution to journalArticle

Oguchi, Yusuke ; Mikhailenko, Sergey ; Ohki, Takashi ; Olivares, Adrian O. ; De La Cruz, Enrique M. ; Ishiwata, Shin'ichi. / Load-dependent ADP binding to myosins V and VI : Implications for subunit coordination and function. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 22. pp. 7714-7719.
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AU - De La Cruz, Enrique M.

AU - Ishiwata, Shin'ichi

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