Are coiled-coils of dimeric kinesins unwound during their walking on microtubule?
Are coiled-coils of dimeric kinesins unwound during their walking on microtubule?
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二聚体驱动蛋白的卷曲螺旋在微管上行走时是否解开？
DOI：
10.1371/journal.pone.0036071
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wang PY
中科院分区：
文献类型：
--
作者：
Duan ZW;Xie P;Li W;Wang PY
二聚体运动蛋白，如同二聚体运动蛋白-1、同二聚体运动蛋白Ncd和异二聚体运动蛋白Kar3/ vik1由两个头部结构域组成，它们通过一根棒状的线圈状茎连接在一起。尽管对二聚体的结构、动力学、动力学和行走机理进行了广泛而深入的研究，但其盘绕线圈在微管上行走时是否解绕仍是一个不清楚的问题。在这里，我们试图通过分子动力学模拟来澄清这个问题。我们的模拟结果表明，对于Ncd，只需几对残差就可以将线圈展开，平均力势的变化很大。对于Ncd和激酶-1，启动盘绕线圈解绕所需的力大于展开形成盘绕线圈的单螺旋所需的力，或者大于展开DNA双链所需的力，这高于在强微管结合状态下激酶蛋白头从微管解束缚的力。根据这些结果，并将Kar3/Vik1的线圈序列与Ncd和kinesin-1的线圈序列进行比较，可以推断Kar3/Vik1的线圈也应该是非常稳定的。因此，我们得出了kinesin-1、Ncd和Kar3/Vik1的盘绕线圈在微管上行走时几乎不可能展开的结论。
Dimeric kinesin motor proteins such as homodimeric kinesin-1, homodimeric Ncd and heterodimeric Kar3/Vik1are composed of two head domains which are connected together by a rod-shaped, coiled-coil stalk. Despite the extensive and intensive studies on structures, kinetics, dynamics and walking mechanism of the dimers, whether their coiled-coils are unwound or not during their walking on the microtubule is still an unclear issue. Here, we try to clarify this issue by using molecular dynamics simulations. Our simulation results showed that, for Ncd, a large change in potential of mean force is required to unwind the coiled-coil by only several pairs of residues. For both Ncd and kinesin-1, the force required to initiate the coiled-coil unwinding is larger than that required for unfolding of the single -helix that forms the coiled-coil or is larger than that required to unwind the DNA duplex, which is higher than the unbinding force of the kinesin head from the microtubule in strong microtubule-binding states. Based on these results and the comparison of the sequence between the coiled-coil of Kar3/Vik1 and those of Ncd and kinesin-1, it was deduced that the coiled-coil of the Kar3/Vik1 should also be very stable. Thus, we concluded that the coiled-coils of kinesin-1, Ncd and Kar3/Vik1 are almost impossible to unwind during their walking on the microtubule.
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影响因子：
64.5
作者：
Allingham, John S.;Sproul, Lisa R.;Gilbert, Susan P.
通讯作者：
Gilbert, Susan P.
DOI：
10.1073/pnas.94.22.11935
发表时间：
1997-10-28
影响因子：
11.1
作者：
EssevazRoulet, B;Bockelmann, U;Heslot, F
通讯作者：
Heslot, F
影响因子：
56.9
作者：
Asbury, CL;Fehr, AN;Block, SM
通讯作者：
Block, SM
DOI：
10.1073/pnas.91.15.6865
发表时间：
1994-07-19
影响因子：
11.1
作者：
HACKNEY, DD
通讯作者：
HACKNEY, DD
影响因子：
3.4
作者：
Evans, E;Ritchie, K
通讯作者：
Ritchie, K