Electrostatically biased binding of kinesin to microtubules.
Electrostatically biased binding of kinesin to microtubules.
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DOI：
10.1371/journal.pbio.1001207
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发表时间：
2011-11
期刊：
影响因子：
9.8
通讯作者：
Cross RA
中科院分区：
文献类型：
--
作者：
Grant BJ;Gheorghe DM;Zheng W;Alonso M;Huber G;Dlugosz M;McCammon JA;Cross RA
An electrostatic field rotates, slides, and guides the kinesin head to bind the microtubule at a site a short distance ahead, thus determining the direction of movement of the motor. The minimum motor domain of kinesin-1 is a single head. Recent evidence suggests that such minimal motor domains generate force by a biased binding mechanism, in which they preferentially select binding sites on the microtubule that lie ahead in the progress direction of the motor. A specific molecular mechanism for biased binding has, however, so far been lacking. Here we use atomistic Brownian dynamics simulations combined with experimental mutagenesis to show that incoming kinesin heads undergo electrostatically guided diffusion-to-capture by microtubules, and that this produces directionally biased binding. Kinesin-1 heads are initially rotated by the electrostatic field so that their tubulin-binding sites face inwards, and then steered towards a plus-endwards binding site. In tethered kinesin dimers, this bias is amplified. A 3-residue sequence (RAK) in kinesin helix alpha-6 is predicted to be important for electrostatic guidance. Real-world mutagenesis of this sequence powerfully influences kinesin-driven microtubule sliding, with one mutant producing a 5-fold acceleration over wild type. We conclude that electrostatic interactions play an important role in the kinesin stepping mechanism, by biasing the diffusional association of kinesin with microtubules. Animal and plant cells contain a molecular-scale “railway” network, in which the tracks, called microtubules, radiate out from the cell centre and locomotive proteins, called kinesins, haul their molecular cargoes along the microtubule tracks. This railway system transports many different cargoes to where they are needed, so it is crucial for the cell's organization and function. Breakdowns in this transport system can cause diseases like Alzheimer's, and drugs that temporarily halt transport make powerful anti-cancer agents. Precisely how kinesin motor proteins move along their microtubule tracks is an important question in biology. We know that some kinesins have twin “heads” that alternately bind to and step along microtubules in a coordinated walking action. But more usually, kinesins have only one head. How single-headed kinesins produce force and movement is poorly understood. In this study, we address this question and show that electrical attraction between single kinesin heads and microtubules is a critical factor deciding the direction of movement: each time the head approaches a microtubule, it slides forwards by the electrical attraction between the engine and the track.
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影响因子：
5.6
作者：
Grant, Barry J.;McCammon, J. Andrew;Cross, Robert A.
通讯作者：
Cross, Robert A.
DOI：
10.1073/pnas.252409199
发表时间：
2002-12-10
影响因子：
11.1
作者：
Kaseda, K;Higuchi, H;Hirose, K
通讯作者：
Hirose, K
影响因子：
5.6
作者：
Bodey, Andrew J.;Kikkawa, Masahide;Moores, Carolyn A.
通讯作者：
Moores, Carolyn A.
影响因子：
8.6
作者：
ASTUMIAN, RD;BIER, M
通讯作者：
BIER, M
ATP栅极控制驱动蛋白1的束缚头微管蛋白结合。
影响因子：
56.9
作者：
Alonso, Maria C.;Drummond, Douglas R.;Kain, Susan;Hoeng, Julia;Amos, Linda;Cross, Robert A.
通讯作者：
Cross, Robert A.