主页 > 医学动态 >
【Cell】Cell：发现驱动蛋白新功能
研究人员对一个被称为NOD的蛋白质进行了研究，该蛋白质与驱动蛋白略有联系，为细胞内多种活动提供动力，如胞内运输、信号传递以及细胞分裂。他们首先用X线晶体照相术确定了该蛋白的结构，而后用酶动力学来发现它如何运作。虽然该蛋白质是在果蝇体内发现的，但其研究结果对确定相关蛋白在人体的作用仍然有借鉴意义。
这项在NOD上的研究证明驱动蛋白可以通过一种新的方式发挥作用。NOD蛋白质并不移动自己，而是骑在微管的两端，这导致的结果是，在染色体长臂和纺锤体微管之间形成了一个动态的交叉耦合。如果NOD工作异常就会出现这样的结果：分裂后的两个细胞中要么都没有特定的染色体，要么其中的一个出现特定染色体缺失。对细胞和有机体而言，在大多数情况下这都将是致命的。
此前的研究认为，驱动蛋白要么沿着其微管的路径移动，要么使微管分裂。而这项研究为我们介绍了一种驱动蛋白的新型功能，其中NOD并不移动，而是在细胞分裂过程中通过交替收放不断增长的细丝末端来实现移动。这些功能多样蛋白质的发现将会对相关研究产生重大意义。
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. [标签:content1][标签:content2]
阅读本文的人还阅读：
作者:admin@医学,生命科学 2011-08-24 05:11
医学,生命科学网