The Rrp4-exosome complex recruits and channels substrate RNA by a unique mechanism.
The Rrp4-exosome complex recruits and channels substrate RNA by a unique mechanism.
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DOI：
10.1038/nchembio.2328
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发表时间：
2017-05
影响因子：
14.8
通讯作者：
Sprangers R
中科院分区：
文献类型：
--
作者：
Cvetkovic MA;Wurm JP;Audin MJ;Schütz S;Sprangers R
外泌体是参与RNA降解和加工的大型分子机器。在这里，我们解决如何三聚体Rrp 4帽增强古细菌酶复合物的活性。使用甲基TROSY NMR方法，我们在每个Rrp 4原聚体上鉴定了50 μ m长的RNA结合路径。我们表明，Rrp 4帽可以同时招募三个基板，其中之一是在核心降解，而其他两个被定位为随后的降解轮。底物和Rrp 4-外泌体之间的局部相互作用能从复合物的外围向活性位点增加。重要的是，一旦基质进入催化桶，帽和基质之间的固有相互作用强度就减弱，这提供了一种在基质朝向活性位点移动期间减少摩擦的手段。因此，我们的数据揭示了一个复杂的外泌体-底物相互作用机制，使有效的RNA降解。
The exosome is a large molecular machine that is involved in RNA degradation and processing. Here, we address how the trimeric Rrp4 cap enhances the activity of the archaeal enzyme complex. Using methyl TROSY NMR methods we identified a 50 Å long RNA binding path on each Rrp4 protomer. We show that the Rrp4 cap can thus recruit three substrates simultaneously, one of which is degraded in the core while two others are positioned for subsequent degradation rounds. The local interaction energy between the substrate and the Rrp4-exosome increases from the periphery of the complex towards the active sites. Importantly, the intrinsic interaction strength between the cap and the substrate is weakened as soon as substrates enter the catalytic barrel, which provides a means to reduce friction during substrate movements towards the active sites. Our data thus reveal a sophisticated exosome–substrate interaction mechanism that enables efficient RNA degradation.