In search of an optimal ring to couple microtubule depolymerization to processive chromosome motions
In search of an optimal ring to couple microtubule depolymerization to processive chromosome motions
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DOI：
10.1073/pnas.0709524104
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发表时间：
2007-11-27
影响因子：
11.1
通讯作者：
Ataullakhanov, Fazly I.
中科院分区：
文献类型：
--
作者：
Efremov, Artem;Grishchuk, Ekaterina L.;Ataullakhanov, Fazly I.
有丝分裂染色体的运动是由微管（MT）和相关的蛋白质耦合动粒MT结束。一个好的偶联剂应该确保附着的高度稳定性，即使当染色体改变方向或经历很大的反作用力时。最佳的耦合剂也被认为是有效的MT解聚的能量转化为染色体运动。正如几年前所示，一个基于“袖子”的染色体相关结构原则上可以将MT动力学与染色体运动耦合起来。最近发现的一种来自酵母的动粒复合物，"Dam 1"或"DASH"复合物，可能在体内起着环绕偶联物的作用。Dam 1环的某些特征与"套筒“的特征不同，但这些差异是否显著尚未进行研究。在这里，我们从理论上分析了具有Dam 1/DASH复合体特性的环绕耦合器的生物力学特性，例如其大直径和向内延伸。我们证明，如果耦合器被建模为一个宽环的链接，绑定的MT壁，其最佳性能是实现时，连接器是灵活的，他们的结合微管蛋白二聚体是强大的。这种耦合器的扩散运动是有限的，但MT解聚可以通过“强制行走”驱动其运动，其特征与基于偏置扩散的机制显著不同。我们的分析确定了关键的实验参数，其值应确定Dam 1/DASH环是否通过扩散或强制行走移动。
Mitotic chromosome motions are driven by microtubules (MTs) and associated proteins that couple kinetochores to MT ends. A good coupler should ensure a high stability of attachment, even when the chromosome changes direction or experiences a large opposing force. The optimal coupler is also expected to be efficient in converting the energy of MT depolymerization into chromosome motility. As was shown years ago, a '' sleeve ''-based, chromosome-associated structure could, in principle, couple MT dynamics to chromosome motion. A recently identified kinetochore complex from yeast, the '' Dam1 '' or '' DASH '' complex, may function as an encircling coupler in vivo. Some features of the Dam1 ring differ from those of the '' sleeve,'' but whether these differences are significant has not been examined. Here, we analyze theoretically the biomechanical properties of encircling couplers that have properties of the Dam1/DASH complex, such as its large diameter and inward-directed extensions. We demonstrate that, if the coupler is modeled as a wide ring with links that bind the MT wall, its optimal performance is achieved when the linkers are flexible and their binding to tubulin dimers is strong. The diffusive movement of such a coupler is limited, but MT depolymerization can drive its motion via a '' forced walk,'' whose features differ significantly from those of the mechanisms based on biased diffusion. Our analysis identifies key experimental parameters whose values should determine whether the Dam1/DASH ring moves via diffusion or a forced walk.