Nascent Peptide in the Ribosome Exit Tunnel Affects Functional Properties of the A-Site of the Peptidyl Transferase Center
Nascent Peptide in the Ribosome Exit Tunnel Affects Functional Properties of the A-Site of the Peptidyl Transferase Center
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DOI：
10.1016/j.molcel.2010.12.031
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发表时间：
2011-02-04
期刊：
影响因子：
16
通讯作者：
Mankin, Alexander S.
中科院分区：
文献类型：
--
作者：
Ramu, Haripriya;Vazquez-Laslop, Nora;Mankin, Alexander S.
监测新生肽结构和对特定新生肽序列进行功能响应的能力是核糖体的基本性质。这种反应的极端表现是参与基因表达调控的新生肽依赖性核糖体停滞。程序性翻译停滞的分子机制尚不清楚。通过分析核糖体在抗生素抗性基因ermA的调节顺反子处的停滞，我们发现了核糖体出口隧道和肽基转移酶中心（PTC）的A位点在停止翻译中的精心策划的合作。出口通道中诱导抗生素和特定新生肽的存在消除了PTC催化与特定氨基酸子集形成肽键的能力。所赋予的A位点选择性的程度由新生肽的C末端区段调节，其中倒数第三个残基起关键作用。
The ability to monitor the nascent peptide structure and to respond functionally to specific nascent peptide sequences is a fundamental property of the ribosome. An extreme manifestation of such response is nascent peptide-dependent ribosome stalling, involved in the regulation of gene expression. The molecular mechanisms of programmed translation arrest are unclear. By analyzing ribosome stalling at the regulatory cistron of the antibiotic resistance gene ermA, we uncovered a carefully orchestrated cooperation between the ribosomal exit tunnel and the A-site of the peptidyl transferase center (PTC) in halting translation. The presence of an inducing antibiotic and a specific nascent peptide in the exit tunnel abrogate the ability of the PTC to catalyze peptide bond formation with a particular subset of amino acids. The extent of the conferred A-site selectivity is modulated by the C-terminal segment of the nascent peptide, where the third-from-last residue plays a critical role.