Novel NMR Assignment Strategy Reveals Structural Heterogeneity in Solution of the nsP3 HVD Domain of Venezuelan Equine Encephalitis Virus.
Novel NMR Assignment Strategy Reveals Structural Heterogeneity in Solution of the nsP3 HVD Domain of Venezuelan Equine Encephalitis Virus.
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新的NMR分配策略揭示了委内瑞拉马脑炎病毒nsP3 HVD结构域溶液中的结构异质性。
DOI：
10.3390/molecules25245824
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发表时间：
2020-12-10
期刊：
影响因子：
--
通讯作者：
Frolova EI
中科院分区：
文献类型：
--
作者：
Agback P;Shernyukov A;Dominguez F;Agback T;Frolova EI
近年来，内在无序蛋白和无序结构域引起了人们的极大关注。它们中的许多含有线性基序，在形成多组分蛋白质复合物的过程中介导与其他因子的相互作用。核磁共振光谱是一个有价值的工具，用于表征这种类型的相互作用的氨基酸（aa）和原子水平。甲病毒编码非结构蛋白nsP 3，其驱动病毒复制复合物组装。nsP 3蛋白含有超过200-aa-长的高变结构域（HVD），其在不同甲病毒物种之间不显示同源性，被预测为内在无序的，并且似乎对于甲病毒适应不同细胞是关键的。以前，我们已经表明，基孔肯雅病毒（CHIKV）的nsP 3 HVD是完全无序的，形成游离形式的二级结构的趋势较低。在这项新的研究中，我们使用新的NMR方法来分配委内瑞拉马脑炎病毒（VEEV）nsP 3 HVD的光谱。CHIKV和VEEV的HVD没有同源性，但都参与复制复合物的组装和功能。我们发现VEEV nsP 3 HVD也大多是无序的，但在其C-末端片段中含有短的稳定的α-螺旋，其介导与细胞脆性X综合征蛋白家族成员的相互作用。我们的NMR数据还表明，VEEV HVD有几个区域倾向于形成二级结构。
In recent years, intrinsically disordered proteins (IDPs) and disordered domains have attracted great attention. Many of them contain linear motifs that mediate interactions with other factors during formation of multicomponent protein complexes. NMR spectrometry is a valuable tool for characterizing this type of interactions on both amino acid (aa) and atomic levels. Alphaviruses encode a nonstructural protein nsP3, which drives viral replication complex assembly. nsP3 proteins contain over 200-aa-long hypervariable domains (HVDs), which exhibits no homology between different alphavirus species, are predicted to be intrinsically disordered and appear to be critical for alphavirus adaptation to different cells. Previously, we have shown that nsP3 HVD of chikungunya virus (CHIKV) is completely disordered with low tendency to form secondary structures in free form. In this new study, we used novel NMR approaches to assign the spectra for the nsP3 HVD of Venezuelan equine encephalitis virus (VEEV). The HVDs of CHIKV and VEEV have no homology but are both involved in replication complex assembly and function. We have found that VEEV nsP3 HVD is also mostly disordered but contains a short stable α-helix in its C-terminal fragment, which mediates interaction with the members of cellular Fragile X syndrome protein family. Our NMR data also suggest that VEEV HVD has several regions with tendency to form secondary structures.
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影响因子：
3.9
作者：
Gibbs, Eric B.;Cook, Erik C.;Showalter, Scott A.
通讯作者：
Showalter, Scott A.
DOI：
10.1046/j.1432-1327.1998.2560001.x
发表时间：
1998-08-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Markley, JL;Bax, A;Wüthrich, K
通讯作者：
Wüthrich, K
影响因子：
2.7
作者：
Nielsen, Jakob Toudahl;Mulder, Frans A. A.
通讯作者：
Mulder, Frans A. A.
影响因子：
15
作者：
Parigi, Giacomo;Rezaei-Ghaleh, Nasrollah;Luchinat, Claudio
通讯作者：
Luchinat, Claudio
DOI：
10.1016/j.pnmrs.2008.06.002
发表时间：
2009-04-05
影响因子：
6.1
作者：
Mielke, Steven P.;Krishnan, V. V.
通讯作者：
Krishnan, V. V.