The cryo-EM structure of hibernating 100S ribosome dimer from pathogenic Staphylococcus aureus.

The cryo-EM structure of hibernating 100S ribosome dimer from pathogenic Staphylococcus aureus.
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DOI:
10.1038/s41467-017-00753-8
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发表时间:
2017-09-28
影响因子:
16.6
通讯作者:
Yonath AE
Yonath AE
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Matzov D;Aibara S;Basu A;Zimmerman E;Bashan A;Yap MF;Amunts A;Yonath AE

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100 S核糖体二聚体的形成通常与细菌中的翻译抑制有关。反式作用因子核糖体调节因子(RMF)和冬眠促进因子(HPF)直接介导了这一过程。杆菌革兰氏阳性S.金黄色葡萄球菌缺乏RMF同源物,其100 S形成的结构基础尚不清楚。在这里,我们报告的低温电子显微镜结构的天然100 S核糖体从S。金黄色葡萄球菌,揭示其形成的分子机制。该结构不同于先前报道的类似物,并且依赖于HPF C-末端延伸形成两个小核糖体亚基之间相互作用的结合平台。100 S二聚体是通过rRNA h26、h40和蛋白uS 2之间的相互作用形成的,涉及头部和表面区域的构象变化,这些变化可能会阻止RNA聚合酶与核糖体对接。在营养限制的条件下,细菌核糖体经历二聚化,形成无代谢活性的100 S复合物。在这里,作者提出了在革兰氏阳性细菌中形成100 S复合物的结构基础,阐明了核糖体沉默因子抑制翻译的机制。
Formation of 100S ribosome dimer is generally associated with translation suppression in bacteria. Trans-acting factors ribosome modulation factor (RMF) and hibernating promoting factor (HPF) were shown to directly mediate this process in E. coli. Gram-positive S. aureus lacks an RMF homolog and the structural basis for its 100S formation was not known. Here we report the cryo-electron microscopy structure of the native 100S ribosome from S. aureus, revealing the molecular mechanism of its formation. The structure is distinct from previously reported analogs and relies on the HPF C-terminal extension forming the binding platform for the interactions between both of the small ribosomal subunits. The 100S dimer is formed through interactions between rRNA h26, h40, and protein uS2, involving conformational changes of the head as well as surface regions that could potentially prevent RNA polymerase from docking to the ribosome. Under conditions of nutrient limitation, bacterial ribosomes undergo dimerization, forming a 100S complex that is translationally inactive. Here the authors present the structural basis for formation of the 100S complexes in Gram-positive bacteria, shedding light on the mechanism of translation suppression by the ribosome-silencing factors.
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