EMD-26647
SARS-CoV-2 Omicron-BA.2 1-RBD-up Spike Protein Trimer without the P986-P987 stabilizing mutations (S-GSAS-Omicron-BA.2)
EMD-26647
Single-particle3.74 Å
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Map released: 20/04/2022
Last modified: 17/01/2024
Sample Organism:
Homo sapiens
Sample: SARS-CoV-2 S-GSAS-Omicron-BA.2 Spike Ectodomain
Deposition Authors: Stalls V
,
Acharya P
Sample: SARS-CoV-2 S-GSAS-Omicron-BA.2 Spike Ectodomain
Deposition Authors: Stalls V
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Cryo-EM structures of SARS-CoV-2 Omicron BA.2 spike.
Stalls V
,
Lindenberger J,
Gobeil SM,
Henderson R,
Parks R,
Barr M,
Deyton M,
Martin M
,
Janowska K,
Huang X,
May A
,
Speakman M,
Beaudoin E,
Kraft B,
Lu X,
Edwards RJ
,
Eaton A,
Montefiori DC,
Williams WB,
Saunders KO,
Wiehe K,
Haynes BF,
Acharya P
(2022) Cell Rep , 39 , 111009 - 111009
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(2022) Cell Rep , 39 , 111009 - 111009
Abstract:
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.
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.