Switch-based mechanism of kinesin motors

Kinesin motors are specialized enzymes that use hydrolysis of ATP to generate force and movement along their cellular tracks, the microtubules. Although numerous biochemical and biophysical studies have accumulated much data that link microtubule-assisted ATP hydrolysis to kinesin motion, the structural view of kinesin movement remains unclear. This study of the monomeric kinesin motor KIF1A combines X-ray crystallography and cryo-electron microscopy, and allows analysis of force-generating conformational changes at atomic resolution. The motor is revealed in its two functionally critical states-complexed with ADP and with a non-hydrolysable analogue of ATP. The conformational change observed between the ADP-bound and the ATP-like structures of the KIF1A catalytic core is modular, extends to all kinesins and is similar to the conformational change used by myosin motors and G proteins. Docking of the ADP-bound and ATP-like crystallographic models of KIF1A into the corresponding cryo-electron microscopy maps suggests a rationale for the plus-end directional bias associated with the kinesin catalytic core.     

How kinesin waits between steps

Kinesin-1 (conventional kinesin) is a dimeric motor protein that carries cellular cargoes along microtubules by hydrolysing ATP and moving processively in 8-nm steps. The mechanism of processive motility involves the hand-over-hand motion of the two motor domains ('heads'), a process driven by a conformational change in the neck-linker domain of kinesin. However, the 'waiting conformation' of kinesin between steps remains controversial-some models propose that kinesin adopts a one-head-bound intermediate, whereas others suggest that both the kinesin heads are bound to adjacent tubulin subunits. Addressing this question has proved challenging, in part because of a lack of tools to measure structural states of the kinesin dimer as it moves along a microtubule. Here we develop two different single-molecule fluorescence resonance energy transfer (smFRET) sensors to detect whether kinesin is bound to its microtubule track by one or two heads. Our FRET results indicate that, while moving in the presence of saturating ATP, kinesin spends most of its time bound to the microtubule with both heads. However, when nucleotide binding becomes rate-limiting at low ATP concentrations, kinesin waits for ATP in a one-head-bound state and makes brief transitions to a two-head-bound intermediate as it walks along the microtubule. On the basis of these results, we suggest a model for how transitions in the ATPase cycle position the two kinesin heads and drive their hand-over-hand motion.     

Identification of globular mechanochemical heads of kinesin

Kinesin is a mechanoenzyme which uses energy liberated from ATP hydrolysis to transport particles towards the 'plus ends' of microtubules. The enzyme consists of two polypeptide heavy chains of relative molecular mass (Mr) approximately 110,000-140,000 (110K-140K) plus copurifying light chains; these polypeptides are arranged in a structure consisting of two globular heads attached to a fibrous stalk which terminates in a 'feathered' tail. Here we report that a function-disrupting monoclonal antikinesin, which binds to the 45K fragment of the kinesin heavy chain, recognizes an epitope located towards the N-terminal end of the heavy chain, and decorates the two globular heads lying at one end of the intact molecules (one antibody per head). The results show that the two heavy chains of native kinesin are arranged in parallel, and that the 45K fragments, which display nucleotide-sensitive interactions with microtubules, represent mechanochemical 'heads' located at the N-terminal regions of the heavy chains. Thus, it is likely that the kinesin heads are analogous to the subfragment-1 domains of myosin.     

Movement of microtubules by single kinesin molecules

Kinesin is a motor protein that uses energy derived from ATP hydrolysis to move organelles along microtubules. Using a new technique for measuring the movement produced in vitro by individual kinesin molecules, it is shown that a single kinesin molecule can move a microtubule for several micrometers. New information about the mechanism of force generation by kinesin is presented.     

A lever-arm rotation drives motility of the minus-end-directed kinesin Ncd

Kinesins are microtubule-based motor proteins that power intracellular transport. Most kinesin motors, exemplified by Kinesin-1, move towards the microtubule plus end, and the structural changes that govern this directional preference have been described. By contrast, the nature and timing of the structural changes underlying the minus-end-directed motility of Kinesin-14 motors (such as Drosophila Ncd) are less well understood. Using cryo-electron microscopy, here we demonstrate that a coiled-coil mechanical element of microtubule-bound Ncd rotates approximately 70 degrees towards the minus end upon ATP binding. Extending or shortening this coiled coil increases or decreases velocity, respectively, without affecting ATPase activity. An unusual Ncd mutant that lacks directional preference shows unstable nucleotide-dependent conformations of its coiled coil, underscoring the role of this mechanical element in motility. These results show that the force-producing conformational change in Ncd occurs on ATP binding, as in other kinesins, but involves the swing of a lever-arm mechanical element similar to that described for myosins.     

量子力学与经典力学联系的几个例子

文章通过下面几个方面谈量子力学在一定条件下过渡到经典力学处理问题:谐振子与氢原子能级在n→∞时由量子到经典问题的过渡;薛定谔方程在一定条件下转化为哈密顿方程;解薛定谔方程的准经典近似方法。     

量子力学与经典力学联系的几个例子

文章通过下面几个方面谈量子力学在一定条件下过渡到经典力学处理问题:谐振子与氢原子能级在n→∞时由量子到经典问题的过渡;薛定谔方程在一定条件下转化为哈密顿方程;解薛定谔方程的准经典近似方法.     

论经典力学与量子力学中质点的属性

一、经典力学中质点的属性[1]1.牛顿力学中质点的属性唯物主义哲学认为 :时间、空间是运动着的物质的存在形式 ,既没有脱离物质的时空 ,也没有脱离时空的物质。根据唯物主义关于时空的论述 ,物理学中人们对物体运动状态的描述 ,就应包含对物体自身时空特性的描述。物体的运动状态是由物体间的相互作用决定的 ,但描述物体运动状态的自然定律 ,物体在时空中表现的形象特征 ,都必须通过人类的观察发现。观察需要观测信号和观测仪器。现今人类能利用的场信号有4种 :一是电磁场(光) ,二是引力场 ,三是弱力场 ,四是强力场。因此 ,人类认识的物体运…     

牛顿力学的数学系统和力学的相对性原理

本文由牛顿力学的数学系统讨论力学的相对性原理，并以例说明理解力学的相对性原理，一些疑难问题就迎刃而解，否则就会发生错误．     

基于小波变换的分级图像检索

提出了一种基于小波变换的分级图像检索方法,对图像的色彩分量进行Daubechies小波变换,提取低频及高频信息构建特征向量.将查询图像与数据库中图像的特征向量进行方差、不变矩和向量夹角余弦值的分级筛选,取得了较好的检索效果.     

经典力学的相对论化与相对论量子力学

几何光学就是零质量光子的质点力学,而波动光则对应非零质量粒子的波动力学（非相对论的Schroedinger方程）。本从经典力学哈一雅方程的相对论化给出非零质量粒子的狄拉克分量方程及K－G方程。     

A structural change in the kinesin motor protein that drives motility

Kinesin motors power many motile processes by converting ATP energy into unidirectional motion along microtubules. The force-generating and enzymatic properties of conventional kinesin have been extensively studied; however, the structural basis of movement is unknown. Here we have detected and visualized a large conformational change of an approximately 15-amino-acid region (the neck linker) in kinesin using electron paramagnetic resonance, fluorescence resonance energy transfer, pre-steady state kinetics and cryo-electron microscopy. This region becomes immobilized and extended towards the microtubule 'plus' end when kinesin binds microtubules and ATP, and reverts to a more mobile conformation when gamma-phosphate is released after nucleotide hydrolysis. This conformational change explains both the direction of kinesin motion and processive movement by the kinesin dimer.     

简论量子力学的发展

本文分析了量子力学的发展过程 ,从自然辩证法的角度阐述了科学发展的辩证规律 .     

相对论力学中的矛盾

揭示了相对论力学中存在的矛盾.对于一个在S参照纱中静止的孤立体系发生的动力学过程,在与S参照系相对运动的S'参照系中检验时,无论是在S参照系中的同一时刻,还是在S'参照系中的同一时刻,这个过程的动力学结果都不满足动量守恒定律的要求.     

分步规划实施医药销售管理信息化

文章分析了医药企业对销售行业信息管理的需求,阐述了基于B/S架构和移动平台的医药销售信息系统的规划方案,以及如何克服信息系统实施中潜在的障碍和缺陷,并就医药供应链上销售信息的集成问题提出了展望,该方案对于其它行业采用信息技术辅助销售管理同样也有参考价值.