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Structural biology of coronavirus ion channels
Acta Crystallographica Section D ( IF 2.2 ) Pub Date : 2021-04-07 , DOI: 10.1107/s2059798321001431
Francisco J. Barrantes

Viral infection compromises specific organelles of the cell and readdresses its functional resources to satisfy the needs of the invading body. Around 70% of the coronavirus positive‐sense single‐stranded RNA encodes proteins involved in replication, and these viruses essentially take over the biosynthetic and transport mechanisms to ensure the efficient replication of their genome and trafficking of their virions. Some coronaviruses encode genes for ion‐channel proteins – the envelope protein E (orf4a), orf3a and orf8 – which they successfully employ to take control of the endoplasmic reticulum–Golgi complex intermediate compartment or ERGIC. The E protein, which is one of the four structural proteins of SARS‐CoV‐2 and other coronaviruses, assembles its transmembrane protomers into homopentameric channels with mild cationic selectivity. Orf3a forms homodimers and homotetramers. Both carry a PDZ‐binding domain, lending them the versatility to interact with more than 400 target proteins in infected host cells. Orf8 is a very short 29‐amino‐acid single‐passage transmembrane peptide that forms cation‐selective channels when assembled in lipid bilayers. This review addresses the contribution of biophysical and structural biology approaches that unravel different facets of coronavirus ion channels, their effects on the cellular machinery of infected cells and some structure–functional correlations with ion channels of higher organisms.

中文翻译:

冠状病毒离子通道的结构生物学

病毒感染会损害细胞的特定细胞器,并重新分配其功能性资源,以满足入侵者的需求。大约70%的冠状病毒正链单链RNA编码参与复制的蛋白质,这些病毒实质上接管了生物合成和运输机制,以确保其基因组的有效复制和病毒粒子的运输。一些冠状病毒编码离子通道蛋白的基因-包膜蛋白E(orf4a),orf3a和orf8,它们成功地用于控制内质网-高尔基复合体中间区室或ERGIC。E蛋白是SARS-CoV-2和其他冠状病毒的四种结构蛋白之一,它以轻度的阳离子选择性将其跨膜启动子组装成同五聚体通道。Orf3a形成同型二聚体和同型四聚体。两者都带有PDZ结合域,使其具有多功能性,可与受感染宿主细胞中的400多种靶蛋白相互作用。Orf8是一种非常短的29个氨基酸的单通道跨膜肽,在脂质双层中组装时会形成阳离子选择性通道。这篇综述阐述了揭示冠状病毒离子通道不同方面的生物物理和结构生物学方法的贡献,它们对被感染细胞的细胞机制的影响以及与高级生物的离子通道的某些结构-功能相关性。Orf8是一种非常短的29个氨基酸的单通道跨膜肽,在脂质双层中组装时会形成阳离子选择性通道。这篇综述阐述了揭示冠状病毒离子通道不同方面的生物物理和结构生物学方法的贡献,它们对被感染细胞的细胞机制的影响以及与高级生物的离子通道的某些结构-功能相关性。Orf8是一种非常短的29个氨基酸的单通道跨膜肽,在脂质双层中组装时会形成阳离子选择性通道。这篇综述阐述了揭示冠状病毒离子通道不同方面的生物物理和结构生物学方法的贡献,它们对被感染细胞的细胞机制的影响以及与高级生物的离子通道的某些结构-功能相关性。
更新日期:2021-04-08
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