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TitleSARS-CoV-2 Omicron XBB lineage spike structures, conformations, antigenicity, and receptor recognition.
Journal, issue, pagesMol Cell, Vol. 84, Issue 14, Page 2747-22764.e7, Year 2024
Publish dateJul 25, 2024
AuthorsQianyi E Zhang / Jared Lindenberger / Ruth J Parsons / Bhishem Thakur / Rob Parks / Chan Soo Park / Xiao Huang / Salam Sammour / Katarzyna Janowska / Taylor N Spence / Robert J Edwards / Mitchell Martin / Wilton B Williams / Sophie Gobeil / David C Montefiori / Bette Korber / Kevin O Saunders / Barton F Haynes / Rory Henderson / Priyamvada Acharya /
PubMed AbstractA recombinant lineage of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, named XBB, appeared in late 2022 and evolved descendants that successively swept local and ...A recombinant lineage of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, named XBB, appeared in late 2022 and evolved descendants that successively swept local and global populations. XBB lineage members were noted for their improved immune evasion and transmissibility. Here, we determine cryoelectron microscopy (cryo-EM) structures of XBB.1.5, XBB.1.16, EG.5, and EG.5.1 spike (S) ectodomains to reveal reinforced 3-receptor binding domain (RBD)-down receptor-inaccessible closed states mediated by interprotomer RBD interactions previously observed in BA.1 and BA.2. Improved XBB.1.5 and XBB.1.16 RBD stability compensated for stability loss caused by early Omicron mutations, while the F456L substitution reduced EG.5 RBD stability. S1 subunit mutations had long-range impacts on conformation and epitope presentation in the S2 subunit. Our results reveal continued S protein evolution via simultaneous optimization of multiple parameters, including stability, receptor binding, and immune evasion, and the dramatic effects of relatively few residue substitutions in altering the S protein conformational landscape.
External linksMol Cell / PubMed:39059371 / PubMed Central
MethodsEM (single particle)
Resolution3.0 - 4.4 Å
Structure data

EMDB-42302, PDB-8uir:
SARS-CoV-2 Omicron-XBB.1.16 3-RBD down Spike Protein Trimer consensus (S-GSAS-Omicron-XBB.1.16)
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-42342, PDB-8uk1:
SARS-CoV-2 Omicron-XBB.1.16 3-RBD-down Spike Protein Trimer consensus (S-RRAR-Omicron-XBB.1.16)
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-42860, PDB-8v0l:
SARS-CoV-2 Omicron-XBB.1.16 3-RBD-down Spike Protein Trimer 1 (S-RRAR-Omicron-XBB.1.16)
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-42861, PDB-8v0m:
SARS-CoV-2 Omicron-XBB.1.16 3-RBD-down Spike Protein Trimer 2 (S-RRAR-Omicron-XBB.1.16)
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-42862, PDB-8v0n:
SARS-CoV-2 Omicron-XBB.1.16 3-RBD-down Spike Protein Trimer 3 (S-RRAR-Omicron-XBB.1.16)
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-42863, PDB-8v0o:
SARS-CoV-2 Omicron-XBB.1.16 3-RBD down Spike Protein Trimer 1 (S-GSAS-Omicron-XBB.1.16)
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-42864, PDB-8v0p:
SARS-CoV-2 Omicron-XBB.1.16 3-RBD down Spike Protein Trimer 2 (S-GSAS-Omicron-XBB.1.16)
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-42866, PDB-8v0q:
SARS-CoV-2 Omicron-XBB.1.16 3-RBD down Spike Protein Trimer 3 (S-GSAS-Omicron-XBB.1.16)
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-42867, PDB-8v0r:
SARS-CoV-2 Omicron-XBB.1.5 3-RBD down Spike Protein Trimer 1 (S-GSAS-Omicron-XBB.1.5)
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-42868, PDB-8v0s:
SARS-CoV-2 Omicron-XBB.1.5 3-RBD down Spike Protein Trimer 2 (S-GSAS-Omicron-XBB.1.5)
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-42869, PDB-8v0t:
SARS-CoV-2 Omicron-XBB.1.5 3-RBD down Spike Protein Trimer 3 (S-GSAS-Omicron-XBB.1.5)
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-42870, PDB-8v0u:
SARS-CoV-2 Omicron-XBB.1.5 3-RBD down Spike Protein Trimer 4 (S-GSAS-Omicron-XBB.1.5)
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-42871, PDB-8v0v:
SARS-CoV-2 Omicron-EG.5 3-RBD down Spike Protein Trimer 1 (S-GSAS-Omicron-EG.5)
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-42872, PDB-8v0w:
SARS-CoV-2 Omicron-EG.5 3-RBD down Spike Protein Trimer 2 (S-GSAS-Omicron-EG.5)
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-42873, PDB-8v0x:
SARS-CoV-2 Omicron-EG.5 3-RBD down Spike Protein Trimer 3 (S-GSAS-Omicron-EG.5)
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-43421: SARS-CoV-2 Omicron-XBB.1.5 1-RBD up Spike Protein Trimer consensus (S-GSAS-Omicron-XBB.1.5)
Method: EM (single particle) / Resolution: 3.46 Å

EMDB-43422: SARS-CoV-2 Omicron-XBB.1.5 1-RBD up Spike Protein Trimer 1 (S-GSAS-Omicron-XBB.1.5)
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-43423: SARS-CoV-2 Omicron-XBB.1.5 1-RBD up Spike Protein Trimer 2 (S-GSAS-Omicron-XBB.1.5)
Method: EM (single particle) / Resolution: 4.0 Å

EMDB-43450: SARS-CoV-2 Omicron-XBB.1.16 1-RBD up Spike Protein Trimer consensus (S-GSAS-Omicron-XBB.1.16)
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-43451: SARS-CoV-2 Omicron-XBB.1.16 1-RBD up Spike Protein Trimer 1 (S-GSAS-Omicron-XBB.1.16)
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-43452: SARS-CoV-2 Omicron-XBB.1.16 1-RBD up Spike Protein Trimer 2 (S-GSAS-Omicron-XBB.1.16)
Method: EM (single particle) / Resolution: 4.0 Å

EMDB-43453: SARS-CoV-2 Omicron-XBB.1.16 1-RBD up Spike Protein Trimer 3 (S-GSAS-Omicron-XBB.1.16)
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-43460: SARS-CoV-2 Omicron-XBB.1.16 1-RBD-up Spike Protein Trimer (S-RRAR-Omicron-XBB.1.16)
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-43461: SARS-CoV-2 Omicron-XBB.1.16 1.5-RBD-up Spike Protein Trimer 1 (S-RRAR-Omicron-XBB.1.16)
Method: EM (single particle) / Resolution: 4.0 Å

EMDB-43462: SARS-CoV-2 Omicron-XBB.1.16 1.5-RBD-up Spike Protein Trimer 2 (S-RRAR-Omicron-XBB.1.16)
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-43463: SARS-CoV-2 Omicron-EG.5 1-RBD up Spike Protein Trimer (S-GSAS-Omicron-EG.5)
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-43464: SARS-CoV-2 Omicron-EG.5 1.5-RBD up Spike Protein Trimer (S-GSAS-Omicron-EG.5)
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-44000, PDB-9ayw:
SARS-CoV-2 Omicron-EG.5.1 3-RBD down Spike Protein Trimer 1 (S-GSAS-Omicron-EG.5.1)
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-44001, PDB-9ayx:
SARS-CoV-2 Omicron-EG.5.1 3-RBD down Spike Protein Trimer 2 (S-GSAS-Omicron-EG.5.1)
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-44002, PDB-9ayy:
SARS-CoV-2 Omicron-EG.5.1 3-RBD down Spike Protein Trimer 3 (S-GSAS-Omicron-EG.5.1)
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-44003: SARS-CoV-2 Omicron-EG.5.1 1-RBD up Spike Protein Trimer 1 (S-GSAS-Omicron-EG.5.1)
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-44004: SARS-CoV-2 Omicron-EG.5.1 1-RBD up Spike Protein Trimer 2 (S-GSAS-Omicron-EG.5.1)
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-44005: SARS-CoV-2 Omicron-EG.5.1 2-RBD disordered Spike Protein Trimer (S-GSAS-Omicron-EG.5.1)
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-44006: SARS-CoV-2 Omicron-EG.5.1 one S1 disordered Spike Protein Trimer (S-GSAS-Omicron-EG.5.1)
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-44007: SARS-CoV-2 Omicron-EG.5.1 one NTD-RBD disordered Spike Protein Trimer (S-GSAS-Omicron-EG.5.1)
Method: EM (single particle) / Resolution: 4.4 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • severe acute respiratory syndrome coronavirus 2
KeywordsVIRAL PROTEIN / SARS-COV-2 / Glycoprotein / Trimer

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