The kinesin-13 MCAK has an unconventional ATPase cycle adapted for microtubule depolymerization.
The kinesin-13 MCAK has an unconventional ATPase cycle adapted for microtubule depolymerization.
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DOI：
10.1038/emboj.2011.290
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发表时间：
2011-08-26
期刊：
影响因子：
11.4
通讯作者：
Howard, Jonathon
中科院分区：
文献类型：
--
作者：
Friel, Claire T.;Howard, Jonathon
与其他激酶不同，激酶13亚家族的成员不沿微管定向移动，而是解聚微管。为了了解具有结构相似的运动结构域的运动蛋白如何具有如此不同的功能，我们阐明了运动蛋白13 MCAK的ATP周转周期。与易位运动蛋白相反，ATP切割，而不是产物释放，是MCAK ATP周转的限速步骤；未聚合的微管蛋白和微管加速了这一步骤。此外，微管末端通过加速ADP与ATP的交换来充分激活ATP酶。这种周期的调整使MCAK适应其解聚活性：晶格刺激的ATP裂解使MCAK进入弱结合的核苷酸状态，通过扩散到达微管末端，末端特异性的核苷酸交换加速使MCAK进入强结合状态，促进解聚。与沿着微管移动的易位运动蛋白相比，这种改变的周期很好地解释了这种运动蛋白的不同机械行为，它从微管的末端解聚。因此，驱动蛋白运动结构域是一个核苷酸依赖的引擎，可以对运输或解聚功能进行不同的调整。
Unlike other kinesins, members of the kinesin-13 subfamily do not move directionally along microtubules but, instead, depolymerize them. To understand how kinesins with structurally similar motor domains can have such dissimilar functions, we elucidated the ATP turnover cycle of the kinesin-13, MCAK. In contrast to translocating kinesins, ATP cleavage, rather than product release, is the rate-limiting step for ATP turnover by MCAK; unpolymerized tubulin and microtubules accelerate this step. Further, microtubule ends fully activate the ATPase by accelerating the exchange of ADP for ATP. This tuning of the cycle adapts MCAK for its depolymerization activity: lattice-stimulated ATP cleavage drives MCAK into a weakly bound nucleotide state that reaches microtubule ends by diffusion, and end-specific acceleration of nucleotide exchange drives MCAK into a strongly bound state that promotes depolymerization. This altered cycle accounts well for the different mechanical behaviour of this kinesin, which depolymerizes microtubules from their ends, compared to translocating kinesins that walk along microtubules. Thus, the kinesin motor domain is a nucleotide-dependent engine that can be differentially tuned for transport or depolymerization functions.
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DOI：
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