| Autor: |
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 Williams, Kevin O. Saunders, Kevin Wiehe, Barton F. Haynes, Priyamvada Acharya |
| Rok vydání: |
2022 |
| Předmět: |
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| DOI: |
10.1101/2022.04.07.487528 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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