小柯机器人

德国海德堡大学分子生物学中心 Claudio A. P. Joazeiro和Stefan Pfeffer课题组合作取得一项新突破。他们发现MutS DNA修复ATP酶旁系同源物可感知细菌核糖体碰撞。相关论文发表在2022年3月9日出版的《自然》杂志上。

研究人员发现了枯草芽孢杆菌MutS2，它是保守MutS ATP酶家族成员之一，是一种未知的核糖体结合蛋白，在翻译质量控制中具有重要功能；MutS ATP酶家族在DNA损伤修复中发挥功能。对亲和纯化的天然复合物进行冷冻电镜分析，结果表明MutS2在感知停滞和翻译核糖体之间碰撞方面发挥作用，并揭示了核糖体碰撞如何影响下游过程：MutS2具有RNA核酸内切酶小MutS相关(SMR)结构域和可以准确定位以促进核糖体亚基解离的ATP酶/钳结构域，这是核糖体回收和启动核糖体相关蛋白质量控制(RQC)的必要条件。

因此，MutS2以ATP酶结构域依赖的方式促进了丙氨酸尾degrons（RQC的早期步骤）依赖性新生链修饰。MutS2和RQC基因在细菌门中共存的证据佐证了这些观察结果的相关性。总体而言，该研究结果表明，核糖体碰撞在开放阅读框内翻译中断感知方面具有高度保守的作用。

据悉，翻译过程中核糖体停滞不利于细胞适应性，但人们对机体如何感知并引发核糖体亚基循环以及相关mRNA和不完整新生链的质量控制却知之甚少。

附：英文原文

Title: Bacterial ribosome collision sensing by a MutS DNA repair ATPase paralogue

Author: Cerullo, Federico, Filbeck, Sebastian, Patil, Pratik Rajendra, Hung, Hao-Chih, Xu, Haifei, Vornberger, Julia, Hofer, Florian W., Schmitt, Jaro, Kramer, Guenter, Bukau, Bernd, Hofmann, Kay, Pfeffer, Stefan, Joazeiro, Claudio A. P.

Issue&Volume: 2022-03-09

Abstract: Ribosome stalling during translation is detrimental to cellular fitness, but how this is sensed and elicits recycling of ribosomal subunits and quality control of associated mRNA and incomplete nascent chains is poorly understood1,2. Here we uncover Bacillus subtilis MutS2, a member of the conserved MutS family of ATPases that function in DNA mismatch repair3, as an unexpected ribosome-binding protein with an essential function in translational quality control. Cryo-electron microscopy analysis of affinity-purified native complexes shows that MutS2 functions in sensing collisions between stalled and translating ribosomes and suggests how ribosome collisions can serve as platforms to deploy downstream processes: MutS2 has an RNA endonuclease small MutS-related (SMR) domain, as well as an ATPase/clamp domain that is properly positioned to promote ribosomal subunit dissociation, which is a requirement both for ribosome recycling and for initiation of ribosome-associated protein quality control (RQC). Accordingly, MutS2 promotes nascent chain modification with alanine-tail degrons—an early step in RQC—in an ATPase domain-dependent manner. The relevance of these observations is underscored by evidence of strong co-occurrence of MutS2 and RQC genes across bacterial phyla. Overall, the findings demonstrate a deeply conserved role for ribosome collisions in mounting a complex response to the interruption of translation within open reading frames.

DOI: 10.1038/s41586-022-04487-6

Source: https://www.nature.com/articles/s41586-022-04487-6

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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