Cryo-EM structures of SARS-CoV-2 Omicron BA.2 spike.
Cryo-EM structures of SARS-CoV-2 Omicron BA.2 spike.
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DOI：
10.1016/j.celrep.2022.111009
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发表时间：
2022-06-28
期刊：
影响因子：
8.8
通讯作者：
Acharya, Priyamvada
中科院分区：
文献类型：
--
作者：
Stalls, Victoria;Lindenberger, Jared;Gobeil, Sophie M. -C.;Henderson, Rory;Parks, Rob;Barr, Maggie;Deyton, Margaret;Martin, Mitchell;Janowska, Katarzyna;Huang, Xiao;May, Aaron;Speakman, Micah;Beaudoin, Esther;Kraft, Bryan;Lu, Xiaozhi;Edwards, Robert J.;Eaton, Amanda;Montefiori, David C.;Williams, Wilton B.;Saunders, Kevin O.;Wiehe, Kevin;Haynes, Barton F.;Acharya, Priyamvada
严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）组粒BA.2亚谱系相对于BA.1的比例增加。由于刺突(S)蛋白的变化可能是其病理生物学差异的基础，因此我们在这里确定了BA.2 S外畴的冷冻电镜（cro - em）结构，并将其与先前确定的BA.1 S结构进行了比较。BA.2受体结合域（RBD）突变诱导RBD结构的重塑，导致更紧密的包装和改善的热稳定性。在封闭的（或3-RBD缺失的）BA.2 S中，蛋白质原体间RBD相互作用增强，而与BA.1相比，融合肽不易被抗体接触。结合和假病毒中和试验揭示了广泛的免疫逃避，同时确定了两种RBD外部表面结合抗体DH1044和DH1193的表位，这些抗体可以中和BA.1和BA.2。综上所述，我们的研究结果表明，通过蛋白质间体RBD-RBD包装来稳定封闭状态是Omicron变体的一个标志，并且表明BA.1和BA.2 S蛋白的关键功能区域存在差异。stals等人测定的Omicron BA.2 S结构表明，重构的RBD环导致了更耐热的RBD，更好地包裹在3-RBD下行尖峰内，并且失去了4类RBD定向抗体结合。增强的刺突稳定性和免疫逃避可能有助于BA.2有效地胜过BA.1。
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. Stalls et al. determine Omicron BA.2 S structures indicating remodeled RBD loops leading to a more thermostable RBD that is better packed within the 3-RBD-down spike and loss of class 4 RBD directed antibody binding. Enhanced spike stability and immune evasion may contribute to BA.2 efficiently outcompeting BA.1.
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影响因子：
8.8
作者：
Cerutti G;Guo Y;Liu L;Liu L;Zhang Z;Luo Y;Huang Y;Wang HH;Ho DD;Sheng Z;Shapiro L
通讯作者：
Shapiro L
影响因子：
8.8
作者：
Meng B;Kemp SA;Papa G;Datir R;Ferreira IATM;Marelli S;Harvey WT;Lytras S;Mohamed A;Gallo G;Thakur N;Collier DA;Mlcochova P;COVID-19 Genomics UK (COG-UK) Consortium;Duncan LM;Carabelli AM;Kenyon JC;Lever AM;De Marco A;Saliba C;Culap K;Cameroni E;Matheson NJ;Piccoli L;Corti D;James LC;Robertson DL;Bailey D;Gupta RK
通讯作者：
Gupta RK
影响因子：
56.9
作者：
McCallum, Matthew;Czudnochowski, Nadine;Rosen, Laura E.;Zepeda, Samantha K.;Bowen, John E.;Walls, Alexandra C.;Hauser, Kevin;Joshi, Anshu;Stewart, Cameron;Dillen, Josh R.;Powell, Abigail E.;Croll, Tristan, I;Nix, Jay;Virgin, Herbert W.;Corti, Davide;Snell, Gyorgy;Veesler, David
通讯作者：
Veesler, David
影响因子：
16
作者：
Gobeil SM;Henderson R;Stalls V;Janowska K;Huang X;May A;Speakman M;Beaudoin E;Manne K;Li D;Parks R;Barr M;Deyton M;Martin M;Mansouri K;Edwards RJ;Eaton A;Montefiori DC;Sempowski GD;Saunders KO;Wiehe K;Williams W;Korber B;Haynes BF;Acharya P
通讯作者：
Acharya P
DOI：
10.1126/science.abi6226
发表时间：
2021-08-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gobeil SM;Janowska K;McDowell S;Mansouri K;Parks R;Stalls V;Kopp MF;Manne K;Li D;Wiehe K;Saunders KO;Edwards RJ;Korber B;Haynes BF;Henderson R;Acharya P
通讯作者：
Acharya P