Met58 and di-acidic motif located at C-terminal region of SARS-CoV-2 ORF6 plays a crucial role in its structural conformations

IF 3.3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry Pub Date : 2024-12-22 DOI:10.1016/j.bpc.2024.107384

Prateek Kumar, Kumar Udit Saumya, Taniya Bhardwaj, Rajanish Giri

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引用次数: 0

Abstract

Despite being mostly neglected in structural biology, the C-terminal Regions (CTRs) are studied to be multifunctional in humans as well as in viruses. Previously, SARS-CoV-2 Spike and NSP1 proteins' CTRs are observed to be disordered, and experimental evidence showed a gain of structure properties in different physiological environments. In this line, we have investigated the structural dynamics of CTR (residues 38–61) of SARS-CoV-2 ORF6 protein, disrupting bidirectional transport between the nucleus and cytoplasm. ORF6-CTR is disordered in nature but doesn't gain any structure in most conditions. As per studies, residue such as Methionine at 58th position in ORF6 is critical for interaction with Rae1-Nup98. Therefore, along with M58, we have identified a few other mutations from the literature and performed extensive structure modelling and dynamics studies using computational simulations. The exciting revelations in CTR models provide evidence of its structural flexibility and possible capabilities to perform multifunctionality inside the host.

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位于SARS-CoV-2 ORF6 c端区的Met58和二酸基序在其结构构象中起着至关重要的作用。

尽管在结构生物学中大多被忽视，但研究表明c -末端区域在人类和病毒中都具有多功能。此前，SARS-CoV-2 Spike和NSP1蛋白的cstr被观察到是无序的，实验证据表明，在不同的生理环境下，其结构特性得到了增强。在这条线上，我们研究了SARS-CoV-2 ORF6蛋白的CTR（残基38-61）的结构动力学，破坏了细胞核和细胞质之间的双向运输。ORF6-CTR本质上是无序的，但在大多数情况下不会获得任何结构。根据研究，ORF6中第58位的蛋氨酸等残基对于与Rae1-Nup98的相互作用至关重要。因此，与M58一起，我们从文献中确定了其他一些突变，并使用计算模拟进行了广泛的结构建模和动力学研究。CTR模型中令人兴奋的发现提供了其结构灵活性和在宿主内执行多功能的可能能力的证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biophysical chemistry 生物-生化与分子生物学

CiteScore

6.10

自引率

10.50%

发文量

121

审稿时长

20 days

期刊介绍： Biophysical Chemistry publishes original work and reviews in the areas of chemistry and physics directly impacting biological phenomena. Quantitative analysis of the properties of biological macromolecules, biologically active molecules, macromolecular assemblies and cell components in terms of kinetics, thermodynamics, spatio-temporal organization, NMR and X-ray structural biology, as well as single-molecule detection represent a major focus of the journal. Theoretical and computational treatments of biomacromolecular systems, macromolecular interactions, regulatory control and systems biology are also of interest to the journal.