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

研究成果: Article

69 引用 (Scopus)

抄録

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.

元の言語English
ページ(範囲)7714-7719
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
105
発行部数22
DOI
出版物ステータスPublished - 2008 6 3

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

ASJC Scopus subject areas

  • Genetics
  • General

これを引用

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.

:: Proceedings of the National Academy of Sciences of the United States of America, 巻 105, 番号 22, 03.06.2008, p. 7714-7719.

研究成果: Article

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. :: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; 巻 105, 番号 22. pp. 7714-7719.
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T2 - Implications for subunit coordination and function

AU - Oguchi, Yusuke

AU - Mikhailenko, Sergey

AU - Ohki, Takashi

AU - Olivares, Adrian O.

AU - De La Cruz, Enrique M.

AU - Ishiwata, Shin'ichi

PY - 2008/6/3

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N2 - 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.

AB - 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.

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