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9MR1

SARS-CoV-2 S2 monomer in complex with R125-61 Fab

Summary for 9MR1
Entry DOI10.2210/pdb9mr1/pdb
EMDB information48548
DescriptorR125-61 Fab Heavy chain, R125-61 Fab Light chain, Spike protein S2, ... (4 entities in total)
Functional Keywordssars-cov-2, spike, s2, covid, monoclonal antibody, complex, viral protein, viral protein-immune system complex, virus
Biological sourceHomo sapiens (human)
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Total number of polymer chains3
Total formula weight77744.30
Authors
Park, S.,Bangaru, B.,Ward, A.B. (deposition date: 2025-01-06, release date: 2025-11-26)
Primary citationChangrob, S.,Yasuhara, A.,Park, S.,Bangaru, S.,Li, L.,Troxell, C.A.,Halfmann, P.J.,Erickson, S.A.,Catanzaro, N.J.,Yuan, M.,Zhou, P.,Huang, M.,Wilbanks, G.D.,McGrath, J.J.C.,Singh, G.,Nelson, S.A.,Fu, Y.,Zheng, N.Y.,Carayannopoulos, S.M.,Dugan, H.L.,Shaw, D.G.,Stamper, C.T.,Madariaga, M.L.L.,Krammer, F.,Andrabi, R.,Burton, D.R.,Ward, A.B.,Wilson, I.A.,Kawaoka, Y.,Wilson, P.C.
Common cold embecovirus imprinting primes broadly neutralizing antibody responses to SARS-CoV-2 S2.
J.Exp.Med., 222:-, 2025
Cited by
PubMed Abstract: The S2 subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike is highly conserved across coronavirus strains and therefore is a potential pan-coronavirus vaccine target. However, antibodies targeting this region are typically non-neutralizing. We report herein that S2-targeting antibodies from patients who recovered from SARS-CoV-2 infection bound only closely related sarbecovirus subgenus strains and, like most known S2 antibodies, none of these were neutralizing. In contrast, first-exposure, severe acutely infected COVID-19 patients predominantly induced back-boosted antibody-secreting cells imprinted against past common cold coronavirus strain OC43 that were cross-reactive to as many as five subgenera of betacoronavirus strains and gave rise to antibodies that were neutralizing and protective. The antibodies targeted two different sites: one defined by competition with stem helix antibodies, and the second to an underdescribed epitope at the apex of S2. These findings suggest that S2-targeted vaccines could strategically exploit controlled OC43 priming followed by SARS-CoV-2 boosting to enhance the breadth and quality of protective antibody responses.
PubMed: 41066082
DOI: 10.1084/jem.20251146
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.59 Å)
Structure validation

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