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Cell：微管结构助力抗癌药物开发

2015-08-10 佚名 生物谷

微管抗癌药物
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微管是直径仅有几纳米的微管蛋白的空心纤维，其可以形成活细胞的骨架并且在细胞分裂的过程中扮演着重要的角色；近日，刊登在Cell上的一篇报告中，来自加利福尼亚大学等处的研究者通过联合研究，将冷冻电镜技术同特殊的成像分析方法进行结合，成功地从原子视野对微管进行了观察，这对于理解微管在末端结合蛋白中的功能提供了一定帮助，而末端结合蛋白则可以调节微管的动态不稳定性。在有丝分裂期间微管可以拆解重新形成纺锤体

微管是直径仅有几纳米的微管蛋白的空心纤维，其可以形成活细胞的骨架并且在细胞分裂的过程中扮演着重要的角色；近日，刊登在Cell上的一篇报告中，来自加利福尼亚大学等处的研究者通过联合研究，将冷冻电镜技术同特殊的成像分析方法进行结合，成功地从原子视野对微管进行了观察，这对于理解微管在末端结合蛋白中的功能提供了一定帮助，而末端结合蛋白则可以调节微管的动态不稳定性。

在有丝分裂期间微管可以拆解重新形成纺锤体，进而被分裂的细胞利用来移动染色体，当染色体迁移发生时，吸附到染色体上的微管必须进行拆解，并且携带染色体到细胞两端。微管的这种动态不稳定性就是其可以从严格的聚合状态或组装的核苷酸状态转化成为复杂的解聚合状态，而这一过程则是通过微管网架的鸟苷三磷酸(GTP)的水解来驱动的。

生物物理学家Eva Nogales指出，我们的研究揭开了末端结合蛋白如何通过结合微管亚单位来促进微管组装，同时还揭示了末端结合蛋白如何通过促进鸟苷三磷酸的水解来促进微管解开。文章中研究者利用冷冻电镜技术，在携带或不携带末端结合蛋白3的不同核苷酸状态下确定了微管的结构，冷冻电镜技术可以使得蛋白样本在液氮下快速冷冻从而展现出其天然的结构。

利用冷冻电镜技术及成像分析方法，研究者获得了分辨率为3.5埃的微管结构，如今研究者正在研究微管聚合及解聚过程中的精细原子结构，来帮助进行微管动态学的完整描述；最后研究者Nogales表示，微管也是主要的抗癌药物的靶点，比如紫杉醇，其可以抑制核苷酸从增长状态向萎缩状态的过度；而更好地理解微管的动态不稳定性如何被调节对于开发新型的抗癌药物或改善当前的抗癌药物提供了一定的希望和帮助。

原文出处：

Rui Zhang, Gregory M.Mechanistic Origin of Microtubule Dynamic Instability and Its Modulation by EB Proteins.cell.2015


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    2016-05-28 智智灵药

    #CEL#

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    2016-03-18 zhaozhouchifen

    #Cell#

    0

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    2015-08-11 flyingeagle77

    #抗癌药物#

    0

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    2015-08-11 sunylz

    #抗癌药#

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    2015-08-11 ms1774076774505970

    #药物开发#

    0