Folding of VemP into translation-arresting secondary structure is driven by the ribosome exit tunnel.
Folding of VemP into translation-arresting secondary structure is driven by the ribosome exit tunnel.
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DOI：
10.1093/nar/gkac038
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发表时间：
2022-02-28
影响因子：
14.9
通讯作者：
Grubmüller H
中科院分区：
文献类型：
--
作者：
Kolář MH;Nagy G;Kunkel J;Vaiana SM;Bock LV;Grubmüller H
核糖体是在细胞中合成蛋白质的基本生物分子复合物。新生蛋白质通过隧道从核糖体中出现，在那里它们可能与隧道壁或小分子（如抗生素）相互作用。这些相互作用可导致翻译停滞，并产生显著的生理后果。在这里，我们研究了由调节肽VemP引起的阻滞，已知VemP在特定条件下在肽基转移酶中心附近的核糖体隧道内形成α-螺旋。我们使用全原子分子动力学模拟的整个核糖体和圆二色光谱研究螺旋形成的驱动力和VemP如何导致翻译停滞。为此，我们比较了VemP在核糖体隧道中的动力学与其在溶液中的动力学。我们表明，VemP肽在水中具有低螺旋倾向，并且该倾向在水和三氟乙醇的混合物中更高。我们认为，核糖体内的螺旋形成是由VemP与隧道的相互作用驱动的，并且VemP的一部分充当锚。这种锚可能会减缓VemP通过通道的进展，从而形成α-螺旋，这会导致伸长停滞。
The ribosome is a fundamental biomolecular complex that synthesizes proteins in cells. Nascent proteins emerge from the ribosome through a tunnel, where they may interact with the tunnel walls or small molecules such as antibiotics. These interactions can cause translational arrest with notable physiological consequences. Here, we studied the arrest caused by the regulatory peptide VemP, which is known to form α-helices inside the ribosome tunnel near the peptidyl transferase center under specific conditions. We used all-atom molecular dynamics simulations of the entire ribosome and circular dichroism spectroscopy to study the driving forces of helix formation and how VemP causes the translational arrest. To that aim, we compared VemP dynamics in the ribosome tunnel with its dynamics in solution. We show that the VemP peptide has a low helical propensity in water and that the propensity is higher in mixtures of water and trifluorethanol. We propose that helix formation within the ribosome is driven by the interactions of VemP with the tunnel and that a part of VemP acts as an anchor. This anchor might slow down VemP progression through the tunnel enabling α-helix formation, which causes the elongation arrest.
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