tetano
Editor, Senior Moderator
Structure
. 2024 Aug 16:S0969-2126(24)00283-1.
doi: 10.1016/j.str.2024.07.020. Online ahead of print. Concerted deletions eliminate a neutralizing supersite in SARS-CoV-2 BA.2.87.1 spike
Helen M E Duyvesteyn[SUP] 1 [/SUP], Aiste Dijokaite-Guraliuc[SUP] 2 [/SUP], Chang Liu[SUP] 2 [/SUP], Piyada Supasa[SUP] 2 [/SUP], Barbara Kronsteiner[SUP] 3 [/SUP], Katie Jeffery[SUP] 4 [/SUP], Lizzie Stafford[SUP] 5 [/SUP], Paul Klenerman[SUP] 6 [/SUP], Susanna J Dunachie[SUP] 7 [/SUP]; PITCH Consortium; Juthathip Mongkolsapaya[SUP] 8 [/SUP], Elizabeth E Fry[SUP] 9 [/SUP], Jingshan Ren[SUP] 10 [/SUP], David I Stuart[SUP] 11 [/SUP], Gavin R Screaton[SUP] 12 [/SUP]
Affiliations
BA.2.87.1 represents a major shift in the BA.2 lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is unusual in having two lengthy deletions of polypeptide in the spike (S) protein, one of which removes a beta-strand. Here we investigate its neutralization by a variety of sera from infected and vaccinated individuals and determine its spike (S) ectodomain structure. The BA.2.87.1 receptor binding domain (RBD) is structurally conserved and the RBDs are tightly packed in an "all-down" conformation with a small rotation relative to the trimer axis as compared to the closest previously observed conformation. The N-terminal domain (NTD) maintains a remarkably similar structure overall; however, the rearrangements resulting from the deletions essentially destroy the so-called supersite epitope and eliminate one glycan site, while a mutation creates an additional glycan site, effectively shielding another NTD epitope. BA.2.87.1 is relatively easily neutralized but acquisition of additional mutations in the RBD could increase antibody escape allowing it to become a dominant sub-lineage.
Keywords: BA.2.87.1; N-terminal domain; SARS-CoV-2; SARS-CoV-2 variants; cryo-EM; neutralization; protein structure; spike protein; structural virology; virus glycoprotein.
. 2024 Aug 16:S0969-2126(24)00283-1.
doi: 10.1016/j.str.2024.07.020. Online ahead of print. Concerted deletions eliminate a neutralizing supersite in SARS-CoV-2 BA.2.87.1 spike
Helen M E Duyvesteyn[SUP] 1 [/SUP], Aiste Dijokaite-Guraliuc[SUP] 2 [/SUP], Chang Liu[SUP] 2 [/SUP], Piyada Supasa[SUP] 2 [/SUP], Barbara Kronsteiner[SUP] 3 [/SUP], Katie Jeffery[SUP] 4 [/SUP], Lizzie Stafford[SUP] 5 [/SUP], Paul Klenerman[SUP] 6 [/SUP], Susanna J Dunachie[SUP] 7 [/SUP]; PITCH Consortium; Juthathip Mongkolsapaya[SUP] 8 [/SUP], Elizabeth E Fry[SUP] 9 [/SUP], Jingshan Ren[SUP] 10 [/SUP], David I Stuart[SUP] 11 [/SUP], Gavin R Screaton[SUP] 12 [/SUP]
Affiliations
- PMID: 39173622
- DOI: 10.1016/j.str.2024.07.020
BA.2.87.1 represents a major shift in the BA.2 lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is unusual in having two lengthy deletions of polypeptide in the spike (S) protein, one of which removes a beta-strand. Here we investigate its neutralization by a variety of sera from infected and vaccinated individuals and determine its spike (S) ectodomain structure. The BA.2.87.1 receptor binding domain (RBD) is structurally conserved and the RBDs are tightly packed in an "all-down" conformation with a small rotation relative to the trimer axis as compared to the closest previously observed conformation. The N-terminal domain (NTD) maintains a remarkably similar structure overall; however, the rearrangements resulting from the deletions essentially destroy the so-called supersite epitope and eliminate one glycan site, while a mutation creates an additional glycan site, effectively shielding another NTD epitope. BA.2.87.1 is relatively easily neutralized but acquisition of additional mutations in the RBD could increase antibody escape allowing it to become a dominant sub-lineage.
Keywords: BA.2.87.1; N-terminal domain; SARS-CoV-2; SARS-CoV-2 variants; cryo-EM; neutralization; protein structure; spike protein; structural virology; virus glycoprotein.