日前,，美國(guó)達(dá)特茅斯學(xué)院的一組研究人員發(fā)現(xiàn)了一種蛋白質(zhì)在參與染色體分離中的新功能。該發(fā)現(xiàn)將有助于進(jìn)一步增加人們對(duì)細(xì)胞基本工作原理的認(rèn)識(shí),，并有助于解釋細(xì)胞功能紊亂現(xiàn)象以及由此產(chǎn)生癌細(xì)胞的過(guò)程,。該學(xué)院和與其一同進(jìn)行該項(xiàng)研究的勞倫斯伯克利國(guó)家實(shí)驗(yàn)室、斯托瓦斯醫(yī)學(xué)研究所以及堪薩斯大學(xué)醫(yī)學(xué)中心已將這項(xiàng)成果發(fā)表在《細(xì)胞》雜志上,。
研究人員對(duì)一個(gè)被稱(chēng)為NOD的蛋白質(zhì)進(jìn)行了研究,，該蛋白質(zhì)與驅(qū)動(dòng)蛋白略有聯(lián)系，為細(xì)胞內(nèi)多種活動(dòng)提供動(dòng)力,，如胞內(nèi)運(yùn)輸,、信號(hào)傳遞以及細(xì)胞分裂。他們首先用X線晶體照相術(shù)確定了該蛋白的結(jié)構(gòu),，而后用酶動(dòng)力學(xué)來(lái)發(fā)現(xiàn)它如何運(yùn)作,。雖然該蛋白質(zhì)是在果蠅體內(nèi)發(fā)現(xiàn)的，但其研究結(jié)果對(duì)確定相關(guān)蛋白在人體的作用仍然有借鑒意義,。
“這項(xiàng)在NOD上的研究證明驅(qū)動(dòng)蛋白可以通過(guò)一種新的方式發(fā)揮作用,。”負(fù)責(zé)該項(xiàng)研究的達(dá)特茅斯學(xué)院博士后杰瑞德·克倫說(shuō)。NOD蛋白質(zhì)并不移動(dòng)自己,，而是騎在微管的兩端,，這導(dǎo)致的結(jié)果是，在染色體長(zhǎng)臂和紡錘體微管之間形成了一個(gè)動(dòng)態(tài)的交叉耦合,。如果NOD工作異常就會(huì)出現(xiàn)這樣的結(jié)果：分裂后的兩個(gè)細(xì)胞中要么都沒(méi)有特定的染色體,，要么其中的一個(gè)出現(xiàn)特定染色體缺失。對(duì)細(xì)胞和有機(jī)體而言,，在大多數(shù)情況下這都將是致命的,。
“此前的研究認(rèn)為,，驅(qū)動(dòng)蛋白要么沿著其微管的路徑移動(dòng)，要么使微管分裂,。”達(dá)特茅斯學(xué)院化學(xué)系副教授喬恩·庫(kù)爾說(shuō),，“而這項(xiàng)研究為我們介紹了一種驅(qū)動(dòng)蛋白的新型功能，其中NOD并不移動(dòng),，而是在細(xì)胞分裂過(guò)程中通過(guò)交替收放不斷增長(zhǎng)的細(xì)絲末端來(lái)實(shí)現(xiàn)移動(dòng),。這些功能多樣蛋白質(zhì)的發(fā)現(xiàn)將會(huì)對(duì)相關(guān)研究產(chǎn)生重大意義。”（生物谷Bioon.com）
生物谷推薦原始出處：
Cell, Volume 136, 9 January 2009 doi:10.1016/j.cell.2008.11.048
ATPase Cycle of the Nonmotile Kinesin NOD Allows Microtubule End Tracking and Drives Chromosome Movement
Jared C. Cochran1,Charles V. Sindelar2,Natasha K. Mulko1,Kimberly A. Collins3,Stephanie E. Kong3,R. Scott Hawley3,4andF. Jon Kull1,,
1 Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA
2 Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
3 Stowers Institute for Medical Research, Kansas City, MO 64110, USA
4 Department of Physiology, Kansas University Medical Center, Kansas City, KS 66160, USA
Summary
Segregation of nonexchange chromosomes during Drosophila melanogaster meiosis requires the proper function of NOD, a nonmotile kinesin-10. We have determined the X-ray crystal structure of the NOD catalytic domain in the ADP- and AMPPNP-bound states. These structures reveal an alternate conformation of the microtubule binding region as well as a nucleotide-sensitive relay of hydrogen bonds at the active site. Additionally, a cryo-electron microscopy reconstruction of the nucleotide-free microtubule-NOD complex shows an atypical binding orientation. Thermodynamic studies show that NOD binds tightly to microtubules in the nucleotide-free state, yet other nucleotide states, including AMPPNP, are weakened. Our pre-steady-state kinetic analysis demonstrates that NOD interaction with microtubules occurs slowly with weak activation of ADP product release. Upon rapid substrate binding, NOD detaches from the microtubule prior to the rate-limiting step of ATP hydrolysis, which is also atypical for a kinesin. We propose a model for NOD's microtubule plus-end tracking that drives chromosome movement.
