Clamped-filament elongation model for actin-based motors
Clamped-filament elongation model for actin-based motors
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DOI：
10.1016/s0006-3495(02)75425-8
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发表时间：
2002-02-01
影响因子：
3.4
通讯作者：
Purich, DL
中科院分区：
文献类型：
--
作者：
Dickinson, RB;Purich, DL
虽然肌动蛋白为基础的运动驱动细胞爬行和细胞器和某些病原体的细胞内运动，力产生的潜在机制仍然是一个谜。最近的实验表明，李斯特菌表现出与肌动蛋白丝亚基的周期性相对应的5.4 nm步进运动，以及在间歇性停顿期间极小的位置波动[S. C. Kuo和J.L.麦格拉思。2000.自然407：1026-1029]。这些发现表明，能动细菌在伸长时仍然牢固地结合在肌动蛋白丝末端，这种行为似乎排除了以前的肌动蛋白运动模型。我们提出并分析了一种新的机械化学模型（称为“锁，加载和消防”机制）的力量产生的亲和力调制，夹紧长丝伸长。在锁定步骤期间，细丝的末端含ATP的亚基与位于运动物体表面上的夹子紧密结合;在加载步骤中，肌动蛋白-ATP单体与细丝末端结合，这是触发发射步骤的事件，其中在夹紧的亚基上的ATP水解减弱细丝对夹子的亲和力。这最后一步启动了新的含ATP末端易位到钳位，于是另一个循环重新开始。这个模型解释了表面束缚的细丝如何在运动表面上施加弯曲力或张力的同时生长。此外，模型的随机模拟再现了李斯特菌的签名运动。这种伸长马达，我们称之为actoclampin，利用肌动蛋白的内在ATP酶活性，提供一个简单的，高保真的酶促反应循环，用于力的产生，不需要伸长的细丝从运动表面解离。这种机制可能会运作时，肌动蛋白聚合被要求产生的力量，驱动细胞爬行或细胞内的细胞器运动。
Although actin-based motility drives cell crawling and intracellular locomotion of organelles and certain pathogens, the underlying mechanism of force generation remains a mystery. Recent experiments demonstrated that Listeria exhibit episodes of 5.4-nm stepwise motion corresponding to the periodicity of the actin filament subunits, and extremely small positional fluctuations during the intermittent pauses [S. C. Kuo and J. L. McGrath. 2000. Nature. 407:1026-1029]. These findings suggest that motile bacteria remain firmly bound to actin filament ends as they elongate, a behavior that appears to rule out previous models for actin-based motility. We propose and analyze a new mechanochemical model (called the "Lock, Load & Fire" mechanism) for force generation by means of affinity-modulated, clamped-filament elongation. During the locking step, the filament's terminal ATP-containing subunit binds tightly to a clamp situated on the surface of a motile object; in the loading step, actin-ATP monomer(s) bind to the filament end, an event that triggers the firing step, wherein ATP hydrolysis on the clamped subunit attenuates the filament's affinity for the clamp. This last step initiates translocation of the new ATP-containing terminus to the clamp, whereupon another cycle begins anew. This model explains how surface-tethered filaments can grow while exerting flexural or tensile force on the motile surface. Moreover, stochastic simulations of the model reproduce the signature motions of Listeria. This elongation motor, which we term actoclampin, exploits actin's intrinsic ATPase activity to provide a simple, high-fidelity enzymatic reaction cycle for force production that does not require elongating filaments to dissociate from the motile surface. This mechanism may operate whenever actin polymerization is called upon to generate the forces that drive cell crawling or intracellular organelle motility.