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解析 SARS-CoV-2 5'非翻译区第五元件茎环结构的构象异质性。

Dissecting the Conformational Heterogeneity of Stem-Loop Substructures of the Fifth Element in the 5'-Untranslated Region of SARS-CoV-2.

机构信息

Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt Am Main, Frankfurt/Main, Hessen 60438, Germany.

Center for Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt Am Main, Frankfurt/Main, Hessen 60438, Germany.

出版信息

J Am Chem Soc. 2024 Nov 6;146(44):30139-30154. doi: 10.1021/jacs.4c08406. Epub 2024 Oct 23.

DOI:10.1021/jacs.4c08406
PMID:39442924
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11544613/
Abstract

Throughout the family of coronaviruses, structured RNA elements within the 5' region of the genome are highly conserved. The fifth stem-loop element from SARS-CoV-2 (5_SL5) represents an example of an RNA structural element, repeatedly occurring in coronaviruses. It contains a conserved, repetitive fold within its substructures SL5a and SL5b. We herein report the detailed characterization of the structure and dynamics of elements SL5a and SL5b that are located immediately upstream of the SARS-CoV-2 ORF1a/b start codon. Exploiting the unique ability of solution NMR methods, we show that the structures of both apical loops are modulated by structural differences in the remote parts located in their stem regions. We further integrated our high-resolution models of SL5a/b into the context of full-length 5_SL5 structures by combining different structural biology methods. Finally, we evaluated the impact of the two most common VoC mutations within 5_SL5 with respect to individual base-pair stability.

摘要

在冠状病毒家族中，基因组 5' 区域内的结构 RNA 元件高度保守。来自 SARS-CoV-2 的第五个茎环元件（5_SL5）代表了 RNA 结构元件的一个例子，它在冠状病毒中反复出现。它在其亚结构 SL5a 和 SL5b 内包含一个保守的、重复的折叠。我们在此报告了位于 SARS-CoV-2 ORF1a/b 起始密码子上游的元件 SL5a 和 SL5b 的结构和动态的详细特征。利用溶液 NMR 方法的独特能力，我们表明，两个顶端环的结构都受到其茎区中远程部分结构差异的调节。我们进一步通过结合不同的结构生物学方法，将 SL5a/b 的高分辨率模型整合到全长 5_SL5 结构中。最后，我们评估了 5_SL5 内两个最常见的 VoC 突变对单个碱基对稳定性的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/11544613/25de43fc7e55/ja4c08406_0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/11544613/daaa26b8668d/ja4c08406_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/11544613/e5a9b5cafd8e/ja4c08406_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/11544613/4bc5b2e0eb12/ja4c08406_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/11544613/23323faacafb/ja4c08406_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/11544613/bbcf8b6c6930/ja4c08406_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/11544613/691df655030d/ja4c08406_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/11544613/64282f8b7c96/ja4c08406_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/11544613/7f71dda43276/ja4c08406_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/11544613/5cd3ca4757e4/ja4c08406_0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/11544613/25de43fc7e55/ja4c08406_0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/11544613/daaa26b8668d/ja4c08406_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/11544613/e5a9b5cafd8e/ja4c08406_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/11544613/4bc5b2e0eb12/ja4c08406_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/11544613/23323faacafb/ja4c08406_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/11544613/bbcf8b6c6930/ja4c08406_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/11544613/691df655030d/ja4c08406_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/11544613/64282f8b7c96/ja4c08406_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/11544613/7f71dda43276/ja4c08406_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/11544613/5cd3ca4757e4/ja4c08406_0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/11544613/25de43fc7e55/ja4c08406_0010.jpg

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