Velocity of myosin-based actin sliding depends on attachment and detachment kinetics and reaches a maximum when myosin-binding sites on actin saturate.
Velocity of myosin-based actin sliding depends on attachment and detachment kinetics and reaches a maximum when myosin-binding sites on actin saturate.
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DOI：
10.1016/j.jbc.2021.101178
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Baker JE
中科院分区：
文献类型：
--
作者：
Stewart TJ;Murthy V;Dugan SP;Baker JE
像肌动蛋白和肌球蛋白这样的分子马达经常成组地工作，以产生对许多生物过程至关重要的定向运动和力。虽然人们对单个马达如何产生力和运动知道很多，但令人惊讶的是，人们对多个马达产生的宏观力学背后的机制知之甚少。例如，观察到饱和数量的肌球蛋白头移动肌动蛋白细丝的速度受到肌动蛋白-肌球蛋白附着和脱离动力学的影响，这既不是实验上的解释，也不是理论上的解释。为了更好地理解肌动蛋白-肌球蛋白机械力化学的出现机制，我们使用体外动力分析来测量和关联肌动蛋白滑动速度、肌动蛋白激活的ATPase活性、针对机械负荷的力产生以及细丝速度的钙敏感性。我们的结果表明，速度和ATPase活性都是应变相关的，并且随着肌球蛋白上肌球蛋白结合位点的饱和，速度变得最大，该值取决于附着动力学的40%和脱离动力学的60%。这些结果支持系综马达机械化学的化学热力学模型，并暗示了该框架内的分子显式机制，挑战了独立力产生的假设。
Molecular motors such as kinesin and myosin often work in groups to generate the directed movements and forces critical for many biological processes. Although much is known about how individual motors generate force and movement, surprisingly, little is known about the mechanisms underlying the macroscopic mechanics generated by multiple motors. For example, the observation that a saturating number, N, of myosin heads move an actin filament at a rate that is influenced by actin–myosin attachment and detachment kinetics is accounted for neither experimentally nor theoretically. To better understand the emergent mechanics of actin–myosin mechanochemistry, we use an in vitro motility assay to measure and correlate the N-dependence of actin sliding velocities, actin-activated ATPase activity, force generation against a mechanical load, and the calcium sensitivity of thin filament velocities. Our results show that both velocity and ATPase activity are strain dependent and that velocity becomes maximized with the saturation of myosin-binding sites on actin at a value that is 40% dependent on attachment kinetics and 60% dependent on detachment kinetics. These results support a chemical thermodynamic model for ensemble motor mechanochemistry and imply molecularly explicit mechanisms within this framework, challenging the assumption of independent force generation.
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影响因子：
3.4
作者：
Baker, JE;Brosseau, C;Warshaw, DM
通讯作者：
Warshaw, DM
影响因子：
4.8
作者：
Haldeman, Brian D.;Brizendine, Richard K.;Cremo, Christine R.
通讯作者：
Cremo, Christine R.
影响因子：
64.8
作者：
FINER, JT;SIMMONS, RM;SPUDICH, JA
通讯作者：
SPUDICH, JA
DOI：
10.1073/pnas.95.6.2944
发表时间：
1998-03-17
影响因子：
11.1
作者：
Baker, JE;Brust-Mascher, I;Thomas, DD
通讯作者：
Thomas, DD
DOI：
10.1098/rspb.1938.0050
发表时间：
1938-10-01
期刊：
PROCEEDINGS OF THE ROYAL SOCIETY SERIES B-BIOLOGICAL SCIENCES
影响因子：
--
作者：
Hill, AV
通讯作者：
Hill, AV