Structural insights of a self-assembling 9-residue peptide from the C-terminal tail of the SARS corona virus E-protein in DPC and SDS micelles: A combined high and low resolution spectroscopic study.

Structural insights of a self-assembling 9-residue peptide from the C-terminal tail of the SARS corona virus E-protein in DPC and SDS micelles: A combined high and low resolution spectroscopic study.
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DPC和SDS胶束中SARS Corona病毒E蛋白的C末端尾部的9分组合肽的自组装的结构见解:一项高分辨率和低分辨率光谱研究。

DOI:
10.1016/j.bbamem.2017.10.015
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发表时间:
2018-03
期刊:
Biochimica et biophysica acta. Biomembranes
影响因子:
--
通讯作者:
Bhunia A
Bhunia A
中科院分区:
其他
文献类型:
--
作者:
Ghosh A;Bhattacharyya D;Bhunia A

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近年来,冠状病毒(Coronavirus,CoV)在生理条件下感染冠状病毒的分子机制得到了广泛的研究。在这项研究中,我们已经确定了一个短的,9-残基肽TK 9(T55 VYVYSRVK 63),已从严重急性呼吸综合征(SARS)冠状病毒(SARS CoV)包膜(E)蛋白的羧基端衍生的膜相互作用的机制。的肽已研究了其物理变化的存在下,两性离子DPC和带负电荷的SDS模型膜胶束,分别与电池的生物物理技术,包括二维溶液状态NMR光谱的帮助。有趣的是,在两种胶束环境中,TK 9均采用α螺旋构象;然而,与SDS胶束相比,DPC的螺旋倾向要高得多,表明TK 9对真核细胞膜的特异性比细菌细胞膜更强。肽TK 9的取向在不同的胶束环境中也不同。与细菌膜模拟物相比,肽的亲和力进一步通过其对哺乳动物的显著膜破坏能力来证明。总的来说,TK 9与不同膜环境相互作用的深入结构信息解释了宿主特异性和膜取向,因为随后的膜破坏与病毒发病机制有关。
In recent years, several studies based on the interaction of self-assembling short peptides derived from viroporins with model membranes, have improved our understanding of the molecular mechanism of corona virus (CoV) infection under physiological conditions. In this study, we have characterized the mechanism of membrane interaction of a short, 9-residue peptide TK9 (T55VYVYSRVK63) that had been derived from the carboxyl terminal of the Severe Acute Respiratory Syndrome (SARS) corona virus (SARS CoV) envelope (E) protein. The peptide has been studied for its physical changes in the presence of both zwitterionic DPC and negatively charged SDS model membrane micelles, respectively, with the help of a battery of biophysical techniques including two-dimensional solution state NMR spectroscopy. Interestingly, in both micellar environments, TK9 adopted an alpha helical conformation; however, the helical propensities were much higher in the case of DPC compared to those of SDS micelle, suggesting that TK9 has more specificity towards eukaryotic cell membrane than the bacterial cell membrane. The orientation of the peptide TK9 also varies in the different micellar environments. The peptide's affinity was further manifested by its pronounced membrane disruption ability towards the mammalian compared to the bacterial membrane mimic. Collectively, the in-depth structural information on the interaction of TK9 with different membrane environments explains the host specificity and membrane orientation owing to subsequent membrane disruption implicated in the viral pathogenesis.
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