2012年9月3日 讯 /生物谷BIOON/ --近日，来自田纳西大学的分子生物学家发现了双链RNA分子如何在细胞处于正常状态和疾病状态下被改造修饰。相应的研究成果刊登在了国际著名杂志Nature上，该研究或许为治疗人类某些癌症和病毒感染提供帮助。
在研究中，研究者发现，在古老生命中的DEAD-box蛋白质酶类或许可以像纳米活塞（nanopistons）的重复利用一样来发挥功能，研究者使用化学能量来打开RNA链，随后建立新的结构。研究者Lambowitz表示，在所有有机体的细胞中，RNA在遗传信息的翻译和蛋白质的合成上都扮演着重要的角色，DEAD-box蛋白质是我们所知的最大家族的RNA解链酶，其可以轻松打开RNA链。在某些时候，这些酶类并不行使传统的解链酶的功能。
研究者假设DEAD-box蛋白质可以在不同结构域上发挥功能，蛋白质的一部分结合ATP分子，提供能量；另外第二部分结合双链RNA。一旦第二个结构域结合到了RNA上，那么第一部分就会获得ATP。
研究者在酵母Mss116p中揭示了这种机制，而且这种机制通用于整个蛋白质家族。每一个DEAD-box蛋白质都有着相同的结构，而且其使用相同的机制来发挥作用。在酵母细胞中发现的DEAD-box蛋白质可以识别双链RNA，其对于健康细胞发挥功能至关重要。
在癌症细胞中，其会被“劫持”，高表达DEAD-box蛋白质可以帮助控制失控的癌细胞增殖，并且可以控制细菌、病毒或者真菌引发的感染。后期研究者将深入研究为何DEAD-box蛋白质以癌症或者感染为靶点来发挥作用。（生物谷Bioon.com）
编译自：Ancient Enzymes Function Like Nanopistons to Unwind RNA
doi:10.1038/nature11402
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PMID:
Structural basis for RNA-duplex recognition and unwinding by the DEAD-box helicase Mss116p
Anna L. Mallam, Mark Del Campo, Benjamin Gilman, David J. Sidote & Alan M. Lambowitz
DEAD-box proteins are the largest family of nucleic acid helicases, and are crucial to RNA metabolism throughout all domains of life1, 2. They contain a conserved ‘helicase core’ of two RecA-like domains (domains (D)1 and D2), which uses ATP to catalyse the unwinding of short RNA duplexes by non-processive, local strand separation3. This mode of action differs from that of translocating helicases and allows DEAD-box proteins to remodel large RNAs and RNA–protein complexes without globally disrupting RNA structure4. However, the structural basis for this distinctive mode of RNA unwinding remains unclear. Here, structural, biochemical and genetic analyses of the yeast DEAD-box protein Mss116p indicate that the helicase core domains have modular functions that enable a novel mechanism for RNA-duplex recognition and unwinding. By investigating D1 and D2 individually and together, we find that D1 acts as an ATP-binding domain and D2 functions as an RNA-duplex recognition domain. D2 contains a nucleic-acid-binding pocket that is formed by conserved DEAD-box protein sequence motifs and accommodates A-form but not B-form duplexes, providing a basis for RNA substrate specificity. Upon a conformational change in which the two core domains join to form a ‘closed state’ with an ATPase active site, conserved motifs in D1 promote the unwinding of duplex substrates bound to D2 by excluding one RNA strand and bending the other. Our results provide a comprehensive structural model for how DEAD-box proteins recognize and unwind RNA duplexes. This model explains key features of DEAD-box protein function and affords a new perspective on how the evolutionarily related cores of other RNA and DNA helicases diverged to use different mechanisms
