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-Structure paper
タイトル | Cryo-EM structures of SARS-CoV-2 Omicron BA.2 spike. |
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ジャーナル・号・ページ | Cell Rep, Vol. 39, Issue 13, Page 111009, Year 2022 |
掲載日 | 2022年6月28日 |
著者 | Victoria Stalls / Jared Lindenberger / Sophie M-C Gobeil / Rory Henderson / Rob Parks / Maggie Barr / Margaret Deyton / Mitchell Martin / Katarzyna Janowska / Xiao Huang / Aaron May / Micah Speakman / Esther Beaudoin / Bryan Kraft / Xiaozhi Lu / Robert J Edwards / Amanda Eaton / David C Montefiori / Wilton B Williams / Kevin O Saunders / Kevin Wiehe / Barton F Haynes / Priyamvada Acharya / |
PubMed 要旨 | 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 ...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. |
リンク | Cell Rep / PubMed:35732171 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.31 - 3.98 Å |
構造データ | EMDB-26433, PDB-7ub0: EMDB-26435, PDB-7ub5: EMDB-26436, PDB-7ub6: EMDB-26643: SARS-CoV-2 Omicron-BA.2 1.5-RBD up Spike Protein Trimer without the P986-P987 stabilizing mutations (S-GSAS-Omicron-BA.2) EMDB-26644: SARS-CoV-2 Omicron-BA.2 1-RBD-up Spike Protein Trimer without the P986-P987 stabilizing mutations (S-GSAS-Omicron-BA.2) EMDB-26647: SARS-CoV-2 Omicron-BA.2 1-RBD-up Spike Protein Trimer without the P986-P987 stabilizing mutations (S-GSAS-Omicron-BA.2) |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRAL PROTEIN / Omicron Spike protein / SARS-CoV-2 / variant of concern / 3-down / Omicron-BA.2 / BA.2 |