Hjelm Rex P, Stone Deborah Bennett, Fletterick Robert J, Mendelson Robert A
Los Alamos Neutron Science Center, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
Acta Crystallogr D Biol Crystallogr. 2010 Nov;66(Pt 11):1218-23. doi: 10.1107/S0907444910021323. Epub 2010 Oct 20.
The kinesin-14, Ncd, is a cellular motor involved in microtubule spindle assembly and contraction during mitosis and meiosis. Like other members of the kinesin superfamily, Ncd consists of two motor heads connected by a linker and a long cargo-carrying stalk. The motor heads hydrolyze ATP to ADP to provide the power stroke that moves them and the cargo along the microtubule. Whereas conventional kinesins move processively along the sense of the microtubule right-handed helix, Ncd moves in the opposite direction, apparently using a different motive mechanism. According to the current model, the microtubule-binding state of Ncd is bound by one head and then released during the motive cycle. This is distinguished from the binding states of conventional kinesins, in which the motor heads are always bound in the motive cycle with alternating one-head and two-head binding. The objective was to determine the extent of binding, the binding states of Ncd in the presence of an ATP analogue, AMPPNP, and whether the binding is cooperative. Small-angle neutron scattering (SANS) of microtubules decorated with a deuterated Ncd construct, Ncd281, in solution containing 42% D(2)O was used. These conditions render the microtubule `invisible' to SANS, while amplifying the SANS from the Ncd constructs. In the presence of AMPPNP, 75% of Ncd281 was not bound. The remainder was bound cooperatively by one of its motor heads to the microtubule.
驱动蛋白-14(Ncd)是一种细胞马达,参与有丝分裂和减数分裂过程中的微管纺锤体组装与收缩。与驱动蛋白超家族的其他成员一样,Ncd由两个通过连接体相连的马达头部和一个长长的携带货物的柄组成。马达头部将ATP水解为ADP,以提供驱动它们和货物沿微管移动的动力冲程。传统驱动蛋白沿微管右手螺旋的方向连续移动,而Ncd则沿相反方向移动,显然使用的是不同的驱动机制。根据当前模型,Ncd的微管结合状态由一个头部结合,然后在驱动周期中释放。这与传统驱动蛋白的结合状态不同,在传统驱动蛋白中,马达头部在驱动周期中始终以单头和双头交替结合的方式结合。目的是确定结合程度、在ATP类似物AMPPNP存在下Ncd的结合状态,以及结合是否具有协同性。使用在含有42%D₂O的溶液中用氘代Ncd构建体Ncd281修饰的微管进行小角中子散射(SANS)。这些条件使微管对SANS“不可见”,同时放大了来自Ncd构建体的SANS。在AMPPNP存在的情况下,75%的Ncd281未结合。其余部分由其一个马达头部协同结合到微管上。