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德国汉堡大学Helge Paternoga等研究人员合作揭示RNase R降解核糖体30S亚基的结构基础。相关论文于2024年2月7日在线发表在《自然》杂志上。

研究人员展示了与3′至5′外切核酸酶核糖核酸酶R（RNase R）相关的，两种不同的核糖体30S亚基降解中间产物的原生结构。这些结构显示，RNase R首先与30S平台结合，促进降解功能上重要的反Shine–Dalgarno序列和解码位点螺旋。然后，当RNase R到达30S亚基的颈部区域时遇到了障碍，30S头部的重大结构重排（包括核糖体蛋白的损失）克服了这一障碍。

RNase R与这一运动平行，利用其N端螺旋-翻转-螺旋结构域作为锚，重新定位到解码位点。体外降解试验表明，头部重排是RNase R的主要动力学障碍，但也表明，仅靠这种酶就足以完全降解30S亚基。总之，这些研究结果为RNase R介导的30S降解提供了一个机理基础，并揭示了RNase R是利用一种涉及结合位点锚定切换的动态机制来靶向孤儿30S亚基。

研究人员表示，蛋白质合成是细胞的一个主要耗能过程，需要控制核糖体的产生和周转。尽管过去几年人们对核糖体生物发生的了解取得了重大进展，但一直缺乏对核糖体降解的结构性了解。

附：英文原文

Title: Structural basis of ribosomal 30S subunit degradation by RNase R

Author: Dimitrova-Paternoga, Lyudmila, Kasvandik, Sergo, Beckert, Bertrand, Granneman, Sander, Tenson, Tanel, Wilson, Daniel N., Paternoga, Helge

Issue&Volume: 2024-02-07

Abstract: Protein synthesis is a major energy-consuming process of the cell that requires the controlled production1,2,3 and turnover4,5 of ribosomes. Although the past few years have seen major advances in our understanding of ribosome biogenesis, structural insight into the degradation of ribosomes has been lacking. Here we present native structures of two distinct small ribosomal 30S subunit degradation intermediates associated with the 3′ to 5′ exonuclease ribonuclease R (RNase R). The structures reveal that RNase R binds at first to the 30S platform to facilitate the degradation of the functionally important anti-Shine–Dalgarno sequence and the decoding-site helix 44. RNase R then encounters a roadblock when it reaches the neck region of the 30S subunit, and this is overcome by a major structural rearrangement of the 30S head, involving the loss of ribosomal proteins. RNase R parallels this movement and relocates to the decoding site by using its N-terminal helix-turn-helix domain as an anchor. In vitro degradation assays suggest that head rearrangement poses a major kinetic barrier for RNase R, but also indicate that the enzyme alone is sufficient for complete degradation of 30S subunits. Collectively, our results provide a mechanistic basis for the degradation of 30S mediated by RNase R, and reveal that RNase R targets orphaned 30S subunits using a dynamic mechanism involving an anchored switching of binding sites.

DOI: 10.1038/s41586-024-07027-6

Source: https://www.nature.com/articles/s41586-024-07027-6

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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