Force production of human cytoplasmic dynein is limited by its processivity
Force production of human cytoplasmic dynein is limited by its processivity
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DOI：
10.1126/sciadv.aaz4295
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发表时间：
2020-04-01
期刊：
影响因子：
13.6
通讯作者：
Gennerich, Arne
中科院分区：
文献类型：
--
作者：
Brenner, Sibylle;Berger, Florian;Gennerich, Arne
细胞质动力蛋白是一种高度复杂的运动蛋白，可产生朝向微管负端的力。使用光镊，我们证明人类动力蛋白的低持续合成能力（在解离前采取多个步骤的能力）由于过早的微管解离而限制了其力的产生。使用高陷阱刚度，使电机每步实现更大的力，我们发现电机的真正最大力（“失速力”）类似于 2 pN。此外，平均力与陷阱刚度图产生了一条在失速力处稳定的双曲曲线。我们推导了一个精确描述该曲线的解析方程，预测失速力和零负载处理能力。该理论模型描述了驱动蛋白电机在低处理能力条件下的行为。我们的工作阐明了人类动力蛋白的真正失速力和加工能力，并为理解和分析弱加工电机的分子电机力产生提供了新的范例。
Cytoplasmic dynein is a highly complex motor protein that generates forces toward the minus end of microtubules. Using optical tweezers, we demonstrate that the low processivity (ability to take multiple steps before dissociating) of human dynein limits its force generation due to premature microtubule dissociation. Using a high trap stiffness whereby the motor achieves greater force per step, we reveal that the motor's true maximal force ("stall force") is similar to 2 pN. Furthermore, an average force versus trap stiffness plot yields a hyperbolic curve that plateaus at the stall force. We derive an analytical equation that accurately describes this curve, predicting both stall force and zero-load processivity.This theoretical model describes the behavior of a kinesin motor under low-processivity conditions. Our work clarifies the true stall force and processivity of human dynein and provides a new paradigm for under-standing and analyzing molecular motor force generation for weakly processive motors.