Modulation of conformational changes in helix 69 mutants by pseudouridine modifications.

Modulation of conformational changes in helix 69 mutants by pseudouridine modifications.
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通过假尿苷修饰调节螺旋 69 突变体的构象变化。

DOI:
10.1016/j.bpc.2015.03.001
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发表时间:
2015-05
影响因子:
3.8
通讯作者:
Chow, Christine S.
Chow, Christine S.
中科院分区:
生物学4区
文献类型:
--
作者:
Jiang, Jun;Kharel, Daya Nidhi;Chow, Christine S.

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23S rRNA 的螺旋 69 (H69) 位于核糖体亚基界面和 mRNA 隧道的中心,参与翻译的关键步骤。核糖体活性受到三种假尿苷修饰的影响,这些修饰调节 H69 的结构和构象行为。为了了解假尿苷的存在与序列变化如何影响 H69,检查了野生型 H69 和代表性突变体(A1912G、U1917C 和 A1919G)的生物物理特性。 NMR 和圆二色光谱的结果表明野生型 H69 和所选突变体的 pH 依赖性结构变化受到假尿苷和环序列的调节。突变对 H69 整体稳定性的影响可以忽略不计,然而,假尿苷在低 pH 条件下稳定 H69。先前的生物学研究表明,H69 诱导构象变化的改变可能会导致功能受损。
Centrally located at the ribosomal subunit interface and mRNA tunnel, helix 69 (H69) from 23S rRNA participates in key steps of translation. Ribosome activity is influenced by three pseudouridine modifications, which modulate the structure and conformational behavior of H69. To understand how H69 is affected by the presence of pseudouridine in combination with sequence changes, the biophysical properties of wild-type H69 and representative mutants (A1912G, U1917C, and A1919G) were examined. Results from NMR and circular dichroism spectroscopy indicate that pH-dependent structural changes of wild-type H69 and the chosen mutants are modulated by pseudouridine and loop sequence. The effects of the mutations on global stability of H69 are negligible, however, pseudouridine stabilizes H69 at low pH conditions. Alterations to induced conformational changes of H69 likely result in compromised function, as indicated by previous biological studies.
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