Crystal Structure of Non-Structural Protein 10 from Severe Acute Respiratory Syndrome Coronavirus-2.

Crystal Structure of Non-Structural Protein 10 from Severe Acute Respiratory Syndrome Coronavirus-2.
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DOI:
10.3390/ijms21197375
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发表时间:
2020-10-06
影响因子:
5.6
通讯作者:
Kozielski F
Kozielski F
中科院分区:
生物学2区
文献类型:
--
作者:
Rogstam A;Nyblom M;Christensen S;Sele C;Talibov VO;Lindvall T;Rasmussen AA;André I;Fisher Z;Knecht W;Kozielski F

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导致冠状病毒病19 (COVID-19)的严重急性呼吸综合征冠状病毒-2 (SARS-CoV-2)于2019年底出现并迅速传播,造成全球大流行,造成严重的社会经济后果。对其RNA基因组的早期测序显示,它与SARS高度相似,可能起源于蝙蝠。SARS- cov -2非结构蛋白10 (nsp10)与SARS同源物具有高度的序列相似性,可结合并刺激nsp14和nsp16的3′~ 5′外核糖核酸酶和2′- o-甲基转移酶活性。本文报道了SARS- cov -2非结合形式nsp10的生物物理特性和1.6 Å分辨率结构,并将其与SARS同源物和与SARS- cov -2 nsp16的复合体结合形式的结构进行了比较。nsp10的晶体结构和溶液行为不仅将为理解SARS-CoV-2 nsp10作为病毒RNA封盖装置核心参与者的作用奠定基础,而且还将为开发nsp10抑制剂(干扰复制-转录复合物和病毒复制的关键功能)提供基础。
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), causing Coronavirus Disease 19 (COVID-19), emerged at the end of 2019 and quickly spread to cause a global pandemic with severe socio-economic consequences. The early sequencing of its RNA genome revealed its high similarity to SARS, likely to have originated from bats. The SARS-CoV-2 non-structural protein 10 (nsp10) displays high sequence similarity with its SARS homologue, which binds to and stimulates the 3′-to-5′ exoribonuclease and the 2′-O-methlytransferase activities of nsps 14 and 16, respectively. Here, we report the biophysical characterization and 1.6 Å resolution structure of the unbound form of nsp10 from SARS-CoV-2 and compare it to the structures of its SARS homologue and the complex-bound form with nsp16 from SARS-CoV-2. The crystal structure and solution behaviour of nsp10 will not only form the basis for understanding the role of SARS-CoV-2 nsp10 as a central player of the viral RNA capping apparatus, but will also serve as a basis for the development of inhibitors of nsp10, interfering with crucial functions of the replication–transcription complex and virus replication.
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