Conformational changes of elongation factor G on the ribosome during tRNA translocation.

Conformational changes of elongation factor G on the ribosome during tRNA translocation.
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DOI:
10.1016/j.cell.2014.11.049
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发表时间:
2015-01-15
期刊:
影响因子:
64.5
通讯作者:
Steitz TA
Steitz TA
中科院分区:
生物学1区
文献类型:
--
作者:
Lin J;Gagnon MG;Bulkley D;Steitz TA

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普遍保守的 GTP 酶延伸因子 G (EF-G) 在肽键形成后催化核糖体上转移 RNA (tRNA) 和信使 RNA (mRNA) 的易位。尽管大量研究表明 EF-G 在易位过程中经历了广泛的构象重排,但与核糖体复合物中的 EF-G 基本上仅存在一种构象的高分辨率结构。在这里,我们报告了 EF-G 的四种原子分辨率晶体结构,它们与易位前和易位后状态下编程的核糖体以及抗生素二酪霉素捕获的核糖体结合。我们在易位前复合物中观察到了以前未见过的 EF-G 构象,该构象被核糖体上的二酪霉素独立捕获。我们的结构提供了对核糖体上 EF-G 采样的构象空间的深入了解,并揭示了 EF-G 从紧凑构象到拉长构象的结构转变促进了核糖体上的 tRNA 易位,而抗生素二酪霉素可以阻止这种转变。
The universally conserved GTPase elongation factor G (EF-G) catalyzes the translocation of transfer RNA (tRNA) and messenger RNA (mRNA) on the ribosome after peptide bond formation. Despite numerous studies suggesting that EF-G undergoes extensive conformational rearrangements during translocation, high resolution structures exist for essentially only one conformation of EF-G in complex with the ribosome. Here, we report four atomic resolution crystal structures of EF-G bound to the ribosome programmed in the pre- and post-translocational states and to the ribosome trapped by the antibiotic dityromycin. We observe a previously unseen conformation of EF-G in the pretranslocation complex, which is independently captured by dityromycin on the ribosome. Our structures provide insights into the conformational space that EF-G samples on the ribosome and reveal that tRNA translocation on the ribosome is facilitated by a structural transition of EF-G from a compact to an elongated conformation, which can be prevented by the antibiotic dityromycin.
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