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 |
| 巻 | 105 |
| 発行部数 | 22 |
| DOI | |
| 出版物ステータス | Published - 2008 6 3 |
Fingerprint
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
}
TY - JOUR
T1 - Load-dependent ADP binding to myosins V and VI
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
Y1 - 2008/6/3
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.
KW - Gating mechanism
KW - Intramolecular load
KW - Molecular motors
KW - Processivity
UR - http://www.scopus.com/inward/record.url?scp=45549095652&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=45549095652&partnerID=8YFLogxK
U2 - 10.1073/pnas.0800564105
DO - 10.1073/pnas.0800564105
M3 - Article
C2 - 18509050
AN - SCOPUS:45549095652
VL - 105
SP - 7714
EP - 7719
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 22
ER -