Cryo-EM structures of SARS-CoV-2 Omicron BA.2 spike

被引：64

作者：

Stalls, Victoria ^{[1
]}

Lindenberger, Jared ^{[1
]}

Gobeil, Sophie M. -C. ^{[1
]}

Henderson, Rory ^{[1
,2
]}

Parks, Rob ^{[1
]}

Barr, Maggie ^{[1
]}

Deyton, Margaret ^{[1
]}

Martin, Mitchell ^{[1
]}

Janowska, Katarzyna ^{[1
]}

Huang, Xiao ^{[1
]}

May, Aaron ^{[1
,3
]}

Speakman, Micah ^{[1
]}

Beaudoin, Esther ^{[1
]}

Kraft, Bryan

Lu, Xiaozhi ^{[1
]}

Edwards, Robert J. ^{[1
,2
]}

Eaton, Amanda ^{[1
]}

Montefiori, David C. ^{[1
,4
]}

Williams, Wilton B. ^{[1
,3
]}

Saunders, Kevin O. ^{[1
]}

Wiehe, Kevin ^{[1
]}

Haynes, Barton F. ^{[1
,2
,5
]}

Acharya, Priyamvada ^{[1
,3
,4
]}

机构：

[1] Duke Human Vaccine Inst, Durham, NC 27710 USA

[2] Duke Univ, Dept Med, Durham, NC 27710 USA

[3] Duke Univ, Dept Biochem, Durham, NC 27710 USA

[4] Duke Univ, Dept Surg, Durham, NC 27710 USA

[5] Duke Univ, Dept Immunol, Durham, NC 27710 USA

来源：

CELL REPORTS | 2022年 / 39卷 / 13期

基金：

美国国家科学基金会;

关键词：

VISUALIZATION;

D O I：

10.1016/j.celrep.2022.111009

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 sub-lineage has gained in proportion relative to BA.1. Because spike (S) protein variations may underlie differences in their pathobiology, here we determine cryoelectron microscopy (cryo-EM) structures of the BA.2 S ectodomain and compare these with previously determined BA.1 S structures. BA.2 receptor-binding domain (RBD) mutations induce remodeling of the RBD structure, resulting in tighter packing and improved thermostability. Interprotomer RBD interactions are enhanced in the closed (or 3-RBD-down) BA.2 S, while the fusion peptide is less accessible to antibodies than in BA.1. Binding and pseudovirus neutralization assays reveal extensive immune evasion while defining epitopes of two outer RBD face-binding antibodies, DH1044 and DH1193, that neutralize both BA.1 and BA.2. Taken together, our results indicate that stabilization of the closed state through interprotomer RBD-RBD packing is a hallmark of the Omicron variant and show differences in key functional regions in the BA.1 and BA.2 S proteins.

引用

页数：19

共 50 条

[1]

Accorsi Emma K., 2004, ENV SCI AMP TECHNOLO, V327, P639, DOI [10.1001/jama.2022.0470, DOI 10.1021/ES049641A]

[2] Real-space refinement in PHENIX for cryo-EM and crystallography [J].

Afonine, Pavel V. ;

Poon, Billy K. ;

Read, Randy J. ;

Sobolev, Oleg V. ;

Terwilliger, Thomas C. ;

Urzhumtsev, Alexandre ;

Adams, Paul D. .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2018, 74 :531-544

[3]

Barnes CO, 2020, CELL, V182, P828, DOI [10.1016/j.cell.2020.06.025, 10.1101/2020.05.28.121533]

[4]

Cameroni E, 2022, NATURE, V602, P664, DOI [10.1038/s41586-021-04386-2, 10.1101/2021.12.12.472269]

[5]

Case JB, 2022, bioRxiv, DOI [10.1101/2022.03.17.484787, 10.1101/2022.03.17.484787, DOI 10.1101/2022.03.17.484787]

[6] Cryo-EM structure of the SARS-CoV-2 Omicron spike [J].

Cerutti, Gabriele ;

Guo, Yicheng ;

Liu, Lihong ;

Liu, Liyuan ;

Zhang, Zhening ;

Luo, Yang ;

Huang, Yiming ;

Wang, Harris H. ;

Ho, David D. ;

Sheng, Zizhang ;

Shapiro, Lawrence .

CELL REPORTS, 2022, 38 (09)

[7] ISOLDE: a physically realistic environment for model building into low-resolution electron-density maps [J].

Croll, Tristan Ian .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2018, 74 :519-530

[8] Structural and functional characterizations of infectivity and immune evasion of SARS-CoV-2 Omicron [J].

Cui, Zhen ;

Liu, Pan ;

Wang, Nan ;

Wang, Lei ;

Fan, Kaiyue ;

Zhu, Qianhui ;

Wang, Kang ;

Chen, Ruihong ;

Feng, Rui ;

Jia, Zijing ;

Yang, Minnan ;

Xu, Ge ;

Zhu, Boling ;

Fu, Wangjun ;

Chu, Tianming ;

Feng, Leilei ;

Wang, Yide ;

Pei, Xinran ;

Yang, Peng ;

Xie, Xiaoliang Sunney ;

Cao, Lei ;

Cao, Yunlong ;

Wang, Xiangxi .

CELL, 2022, 185 (05) :860-+

[9] Cold sensitivity of the SARS-CoV-2 spike ectodomain [J].

Edwards, Robert J. ;

Mansouri, Katayoun ;

Stalls, Victoria ;

Manne, Kartik ;

Watts, Brian ;

Parks, Rob ;

Janowska, Katarzyna ;

Gobeil, Sophie M. C. ;

Kopp, Megan ;

Li, Dapeng ;

Lu, Xiaozhi ;

Mu, Zekun ;

Deyton, Margaret ;

Oguin, Thomas H. ;

Sprenz, Jordan ;

Williams, Wilton ;

Saunders, Kevin ;

Montefiori, David ;

Sempowski, Gregory D. ;

Henderson, Rory ;

Alam, Munir ;

Haynes, Barton F. ;

Acharya, Priyamvada .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2021, 28 (02) :128-+

[10] Features and development of Coot [J].

Emsley, P. ;

Lohkamp, B. ;

Scott, W. G. ;

Cowtan, K. .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 2010, 66 :486-501

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