Structures of SARS-CoV-2 spike protein alert noteworthy sites for the potential approaching variants

Xiaorui Xing; Lei Wang; Zhen Cui; Wangjun Fu; Tao Zheng; Lili Qin; Pingju Ge; Aidong Qian; Nan Wang; Shuai Yuan

doi:10.1016/j.virs.2022.11.003

December 2022

. doi: 10.1016/j.virs.2022.11.003

Citation: Xiaorui Xing, Lei Wang, Zhen Cui, Wangjun Fu, Tao Zheng, Lili Qin, Pingju Ge, Aidong Qian, Nan Wang, Shuai Yuan. Structures of SARS-CoV-2 spike protein alert noteworthy sites for the potential approaching variants .VIROLOGICA SINICA, 2022, 37(6) : 938-941. http://dx.doi.org/10.1016/j.virs.2022.11.003

基于SARS-CoV-2刺突蛋白的结构预警需要注意的潜在突变位点

邢效瑞 ^a,b,c ,
王磊 ^c,d ,
崔震 ^c,d ,
付望俊 ^c,d ,
郑韬 ^c,d ,
秦莉莉 ^e ,
葛萍菊 ^e ,
钱爱东 ^a,b,, ,
王男 ^c,, ,
袁帅 ^f,,

a、吉林农业大学兽医学院, 中国长春, 130118;
b、吉林农业大学动物科技学院吉林省农业生产研究中心动物生产重点实验室, 中国长春, 130118;
c、中国科学院生物物理研究所, 生物大分子国家重点实验室, 中国科学院感染与免疫重点实验室, 中国北京, 100101;
d、中国科学院大学, 中国北京, 100101;
e、北京百普赛斯生物科技股份有限公司, 中国北京, 100101;
f、中国科学院武汉病毒研究所, 病毒学国家重点实验室, 湖北武汉, 430071

通讯作者： 钱爱东, qianaidong0115@163.com; 王男, wangnan161@ibp.ac.cn; 袁帅, yuanshuai@wh.iov.cn
收稿日期： 2022-06-30
录用日期： 2022-11-04

摘要

SARS-CoV-2的流行已经造成了全球数百万人死亡，但同时针对COVID-19病毒突变株（主要是一些关键蛋白，如刺突蛋白上的氨基酸位点突变）流行的疫苗研发速度也是前所未有的。目前已完成的研究主要集中在RBD和NTD上热门突变位点的免疫逃避分子机制，然而对其他位置突变的关注较少。本文我们利用低温冷冻电镜技术解析了Lambda、Mu、C.1.2和B.1.620突变株刺突蛋白的三维结构。我们通过结构分析发现了两个重要的突变位点，分别是残基156-157的缺失和T859N的突变。该缺失造成邻近的β-链变短从而扭曲了片层结构，并导致整个NTD结构域的移动。同时我们还发现T859N位点的突变造成调节刺突蛋白构象变化的动力学障碍。我们的研究结果揭示了两个新的突变位点，提醒我们应更多地关注RBD和NTD以外的突变，特别是位于FPPR和630 loop基序的突变。
- SARS-CoV-2突变株
- , FPPR
- , 630 loop

Structures of SARS-CoV-2 spike protein alert noteworthy sites for the potential approaching variants

Xiaorui Xing ^a,b,c ,
Lei Wang ^c,d ,
Zhen Cui ^c,d ,
Wangjun Fu ^c,d ,
Tao Zheng ^c,d ,
Lili Qin ^e ,
Pingju Ge ^e ,
Aidong Qian ^a,b,, ,
Nan Wang ^c,, ,
Shuai Yuan ^f,,

a College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China;
b College of Animal Science and Technology, Jilin Provincial Engineering Research Center of Animal Probiotics, Key Lab of Animal Production, Product Quality and Security, Joint Laboratory of Modern Agricultural Technology International Cooperation, Ministry of Education, Jilin Agricultural University, Changchun, 130118, China;
c CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China;
d University of Chinese Academy of Sciences, Beijing, 100101, China;
e Acrobiosystems, Beijing, 100101, China;
f State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China

Corresponding author: Aidong Qian, qianaidong0115@163.com Nan Wang, wangnan161@ibp.ac.cn Shuai Yuan, yuanshuai@wh.iov.cn
Received Date: 30 June 2022
Accepted Date: 04 November 2022

Abstract

Highlights
1 Deletion of residues 156–157 warps the neighboring beta-sheet and leads NTD and RBD to shift.
2 T859N stabilizes the packing of the 630 loop motif to make RBD standing transition more difficult.
3 The overall structures of the closed state S complex from different variants resemble each other.
4 Mutations in FPPR may affect the overall structure of the trimeric spike protein.

References
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通讯作者: 陈斌, bchen63@163.com

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沈阳化工大学材料科学与工程学院沈阳 110142

Structures of SARS-CoV-2 spike protein alert noteworthy sites for the potential approaching variants

Corresponding author: Aidong Qian, qianaidong0115@163.com

Corresponding author: Nan Wang, wangnan161@ibp.ac.cn

Corresponding author: Shuai Yuan, yuanshuai@wh.iov.cn

a College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China;

b College of Animal Science and Technology, Jilin Provincial Engineering Research Center of Animal Probiotics, Key Lab of Animal Production, Product Quality and Security, Joint Laboratory of Modern Agricultural Technology International Cooperation, Ministry of Education, Jilin Agricultural University, Changchun, 130118, China;

c CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China;

d University of Chinese Academy of Sciences, Beijing, 100101, China;

e Acrobiosystems, Beijing, 100101, China;

f State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China

Received Date: 30 June 2022

Accepted Date: 04 November 2022

Abstract: Highlights
1 Deletion of residues 156–157 warps the neighboring beta-sheet and leads NTD and RBD to shift.
2 T859N stabilizes the packing of the 630 loop motif to make RBD standing transition more difficult.
3 The overall structures of the closed state S complex from different variants resemble each other.
4 Mutations in FPPR may affect the overall structure of the trimeric spike protein.

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基于SARS-CoV-2刺突蛋白的结构预警需要注意的潜在突变位点

摘要

Structures of SARS-CoV-2 spike protein alert noteworthy sites for the potential approaching variants

Abstract

References

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Electronic Supplementary Material

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通讯作者: 陈斌, bchen63@163.com