Simple mechanochemistry describes the dynamics of kinesin molecules
Simple mechanochemistry describes the dynamics of kinesin molecules
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DOI：
10.1073/pnas.141080498
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发表时间：
2001-07-03
影响因子：
11.1
通讯作者：
Kolomeisky, AB
中科院分区：
文献类型：
--
作者：
Fisher, ME;Kolomeisky, AB
最近，Block和同事[Visscher，K.，施尼策，M。J.，&布洛克，S. M.（1999）Nature（伦敦）400，184-189和Schnitzer，M. J.，Visscher，K. &布洛克，S. M.（2000）Nat. Cell Biol.2，718-723]报道了在受控负荷（F = 1至8 pN，[ATP] = 1 μ M至2 mM）下，在体外沿着沿着微管移动的单个驱动蛋白分子的广泛观察。他们对速度、V随机性、r、失速力和平均运行长度L的测量揭示了需要改进理论理解。我们表明，提出明确的公式，提供了一个定量的基础上比较不同的分子马达，他们的数据令人满意地描述简单，离散状态，顺序随机模型。最简单的（N = 2）状态模型与固定的负载分配因子和动力学速率常数与停流实验一致，占全球（V，F，L，[ATP]）的相互依赖性，并进一步匹配的相对加速度下观察到的辅助负载。随机性r（F，[ATP]）由等待时间分布psi（+）（1）（t）（对于ATP结合后的转变）解释，宽度参数nu等于（2），接近或等于2.5，指示机械性接近或等于0.6或几个（大于或等于nu - 1）进一步，动力学耦合状态：实际上，N = 4（但不是N = 3）模型做得很好。分析表明：（i）ATP结合的d（0）= 1.8-2.1 nm的子步骤（与基于结构的建议一致）;（ii）ATP结合和未结合的相当的负载依赖性;（iii）反向水解和随后的反向速率的强负载依赖性;和（iv）ATP结合后，分离速率的大的（大于或等于50倍）增加，具有显著的负载依赖性。
Recently, Block and coworkers [Visscher, K., Schnitzer, M. J., & Block, S. M. (1999) Nature (London) 400, 184-189 and Schnitzer, M. J., Visscher, K. & Block, S. M. (2000) Nat. Cell Biol. 2, 718-723] have reported extensive observations of individual kinesin molecules moving along microtubules in vitro under controlled loads, F = 1 to 8 pN, with [ATP] = 1 muM to 2 mM. Their measurements of velocity, V randomness, r, stalling force, and mean run length, L, reveal a need for improved theoretical understanding. We show, presenting explicit formulae that provide a quantitative basis for comparing distinct molecular motors, that their data are satisfactorily described by simple, discrete-state, sequential stochastic models. The simplest (N = 2)-state model with fixed load-distribution factors and kinetic rate constants concordant with stopped-flow experiments, accounts for the global (V, F, L, [ATP]) interdependence and, further, matches relative acceleration observed under assisting loads. The randomness, r(F,[ATP]), is accounted for by a waiting-time distribution, psi (+)(1)(t), [for the transition(s) following ATP binding] with a width parameter nu equivalent to (2) similar or equal to 2.5, indicative of a dispersive stroke of mechanicity similar or equal to 0.6 or of a few (greater than or equal to nu - 1) further, kinetically coupled states: indeed, N = 4 (but not N = 3) models do well. The analysis reveals: (i) a substep of d(0) = 1.8-2.1 nm on ATP binding (consistent with structurally based suggestions); (ii) comparable load dependence for ATP binding and unbinding; (iii) a strong load dependence for reverse hydrolysis and subsequent reverse rates; and (iv) a large (greater than or equal to 50-fold) increase in detachment rate, with a marked load dependence, following ATP binding.