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

被引：67

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

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