7UB5

SARS-CoV-2 Omicron-BA.2 3-RBD down Spike Protein Trimer without the P986-P987 stabilizing mutations (S-GSAS-Omicron-BA.2)

Summary for 7UB5

• Entry DOI: 10.2210/pdb7ub5/pdb
• EMDB information: 26435
• Descriptor: Spike glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: omicron spike protein, sars-cov-2, variant of concern, 3-down, viral protein, omicron-ba.2, ba.2
• Biological source: Severe acute respiratory syndrome coronavirus 2
• Total number of polymer chains: 3
• Total formula weight: 437560.11

Authors

Stalls, V.,Acharya, P. (deposition date: 2022-03-14, release date: 2022-04-20, Last modification date: 2024-10-23)

Primary citation

Stalls, V.,Lindenberger, J.,Gobeil, S.M.,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, R.J.,Eaton, A.,Montefiori, D.C.,Williams, W.B.,Saunders, K.O.,Wiehe, K.,Haynes, B.F.,Acharya, P.
Cryo-EM structures of SARS-CoV-2 Omicron BA.2 spike.
Cell Rep, 39:111009-111009, 2022

PubMed 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.

PubMed: 35732171
DOI: 10.1016/j.celrep.2022.111009

Experimental method

ELECTRON MICROSCOPY (3.35 Å)