Translocation kinetics and structural dynamics of ribosomes are modulated by the conformational plasticity of downstream pseudoknots
Translocation kinetics and structural dynamics of ribosomes are modulated by the conformational plasticity of downstream pseudoknots
复制标题
核糖体的易位动力学和结构动力学受下游假结的构象可塑性调节
DOI：
10.1093/nar/gky636
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发表时间：
2018-07
影响因子：
14.9
通讯作者：
Chen C.
中科院分区：
文献类型：
--
作者：
Wu B.;Zhang H.;Sun R.;Peng S.;Cooperman B.S.;Goldman Y.E.;Chen C.
摘要下游稳定的mRNA二级结构可以通过阻碍核糖体上tRNA和mRNA的协同运动来阻止核糖体的伸长。下游mRNA结构的添加，如茎环或假结，对于诱导-1程序性核糖体移码（-1 PRF）是必不可少的。有趣的是，以前的研究表明，-1 PRF效率与假结的构象可塑性相关，定义为它们形成不完全折叠结构的倾向，而不是与假结的机械性能相关。为了阐明易位和-1 PRF的详细分子机制，我们应用了几个smFRET检测系统地研究如何易位率和构象动力学的核糖体受到不同的假结。我们的研究结果表明，初始假结解旋显着抑制后期易位和调节核糖体易位后复合物的构象动力学。假结对核糖体结构动力学的影响与其诱导-1PRF的能力密切相关。我们的研究结果使我们提出一个动力学计划易位，其中包括一个初始的动力冲程步骤和以下的热棘轮步骤。该方案提供了关于通过假结选择性调节后期易位如何影响-1 PRF的机制见解。总的来说，我们的研究结果推进了目前对易位和核糖体诱导的mRNA结构解旋的理解。
Abstract Downstream stable mRNA secondary structures can stall elongating ribosomes by impeding the concerted movements of tRNAs and mRNA on the ribosome during translocation. The addition of a downstream mRNA structure, such as a stem-loop or a pseudoknot, is essential to induce -1 programmed ribosomal frameshifting (-1 PRF). Interestingly, previous studies revealed that -1 PRF efficiencies correlate with conformational plasticity of pseudoknots, defined as their propensity to form incompletely folded structures, rather than with the mechanical properties of pseudoknots. To elucidate the detailed molecular mechanisms of translocation and -1 PRF, we applied several smFRET assays to systematically examine how translocation rates and conformational dynamics of ribosomes were affected by different pseudoknots. Our results show that initial pseudoknot-unwinding significantly inhibits late-stage translocation and modulates conformational dynamics of ribosomal post-translocation complexes. The effects of pseudoknots on the structural dynamics of ribosomes strongly correlate with their abilities to induce -1 PRF. Our results lead us to propose a kinetic scheme for translocation which includes an initial power-stroke step and a following thermal-ratcheting step. This scheme provides mechanistic insights on how selective modulation of late-stage translocation by pseudoknots affects -1 PRF. Overall our findings advance current understanding of translocation and ribosome-induced mRNA structure unwinding.
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影响因子：
6.1
作者：
Agirrezabala, Xabier;Frank, Joachim
通讯作者：
Frank, Joachim
DOI：
10.1261/rna.039792.113
发表时间：
2014-01
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Manickam N;Nag N;Abbasi A;Patel K;Farabaugh PJ
通讯作者：
Farabaugh PJ
编程的核糖体框架从同一基因产生铜转运蛋白和铜伴侣。
影响因子：
16
作者：
Meydan S;Klepacki D;Karthikeyan S;Margus T;Thomas P;Jones JE;Khan Y;Briggs J;Dinman JD;Vázquez-Laslop N;Mankin AS
通讯作者：
Mankin AS
影响因子：
11.4
作者：
Holtkamp, Wolf;Cunha, Carlos E.;Rodnina, Marina V.
通讯作者：
Rodnina, Marina V.
DOI：
10.1073/pnas.1403457111
发表时间：
2014-04-15
影响因子：
11.1
作者：
Kim, Hee-Kyung;Liu, Fei;Tinoco, Ignacio, Jr.
通讯作者：
Tinoco, Ignacio, Jr.