tetano
Editor, Senior Moderator
Cell Rep
. 2022 Jun 8;111009.
doi: 10.1016/j.celrep.2022.111009. Online ahead of print.
Cryo-EM structures of SARS-CoV-2 Omicron BA.2 spike
Victoria Stalls[SUP] 1 [/SUP], Jared Lindenberger[SUP] 1 [/SUP], Sophie M-C Gobeil[SUP] 1 [/SUP], Rory Henderson[SUP] 2 [/SUP], Rob Parks[SUP] 1 [/SUP], Maggie Barr[SUP] 1 [/SUP], Margaret Deyton[SUP] 1 [/SUP], Mitchell Martin[SUP] 1 [/SUP], Katarzyna Janowska[SUP] 1 [/SUP], Xiao Huang[SUP] 1 [/SUP], Aaron May[SUP] 3 [/SUP], Micah Speakman[SUP] 1 [/SUP], Esther Beaudoin[SUP] 1 [/SUP], Bryan Kraft[SUP] 4 [/SUP], Xiaozhi Lu[SUP] 1 [/SUP], Robert J Edwards[SUP] 2 [/SUP], Amanda Eaton[SUP] 1 [/SUP], David C Montefiori[SUP] 5 [/SUP], Wilton B Williams[SUP] 3 [/SUP], Kevin O Saunders[SUP] 5 [/SUP], Kevin Wiehe[SUP] 2 [/SUP], Barton F Haynes[SUP] 6 [/SUP], Priyamvada Acharya[SUP] 7 [/SUP]
Affiliations
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.
Keywords: CP: Microbiology; Omicron BA.2; SARS-CoV-2 spike; cryoelectron microscopy; fusion peptide; immune evasion; receptor binding domain.
. 2022 Jun 8;111009.
doi: 10.1016/j.celrep.2022.111009. Online ahead of print.
Cryo-EM structures of SARS-CoV-2 Omicron BA.2 spike
Victoria Stalls[SUP] 1 [/SUP], Jared Lindenberger[SUP] 1 [/SUP], Sophie M-C Gobeil[SUP] 1 [/SUP], Rory Henderson[SUP] 2 [/SUP], Rob Parks[SUP] 1 [/SUP], Maggie Barr[SUP] 1 [/SUP], Margaret Deyton[SUP] 1 [/SUP], Mitchell Martin[SUP] 1 [/SUP], Katarzyna Janowska[SUP] 1 [/SUP], Xiao Huang[SUP] 1 [/SUP], Aaron May[SUP] 3 [/SUP], Micah Speakman[SUP] 1 [/SUP], Esther Beaudoin[SUP] 1 [/SUP], Bryan Kraft[SUP] 4 [/SUP], Xiaozhi Lu[SUP] 1 [/SUP], Robert J Edwards[SUP] 2 [/SUP], Amanda Eaton[SUP] 1 [/SUP], David C Montefiori[SUP] 5 [/SUP], Wilton B Williams[SUP] 3 [/SUP], Kevin O Saunders[SUP] 5 [/SUP], Kevin Wiehe[SUP] 2 [/SUP], Barton F Haynes[SUP] 6 [/SUP], Priyamvada Acharya[SUP] 7 [/SUP]
Affiliations
- PMID: 35732171
- DOI: 10.1016/j.celrep.2022.111009
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.
Keywords: CP: Microbiology; Omicron BA.2; SARS-CoV-2 spike; cryoelectron microscopy; fusion peptide; immune evasion; receptor binding domain.