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7MXP

Cryo-EM structure of NTD-directed neutralizing antibody LP5 Fab in complex with SARS-CoV-2 S2P spike

Summary for 7MXP
Entry DOI10.2210/pdb7mxp/pdb
EMDB information24075
DescriptorSpike glycoprotein, LP5 Fab Heavy Chain, LP5 Fab Light Chain, ... (7 entities in total)
Functional Keywordsneturalsing antibody, fusion protein, spike glycoprotein, nrd, ntd-directed antibody, lp5, viral protein, immune system, viral protein-immune system complex, viral protein/immune system
Biological sourceSevere acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2)
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Total number of polymer chains9
Total formula weight513955.83
Authors
Reddem, E.R.,Casner, R.G.,Shapiro, L. (deposition date: 2021-05-19, release date: 2022-05-25, Last modification date: 2024-10-30)
Primary citationMadan, B.,Reddem, E.R.,Wang, P.,Casner, R.G.,Nair, M.S.,Huang, Y.,Fahad, A.S.,de Souza, M.O.,Banach, B.B.,Lopez Acevedo, S.N.,Pan, X.,Nimrania, R.,Teng, I.T.,Bahna, F.,Zhou, T.,Zhang, B.,Yin, M.T.,Ho, D.D.,Kwong, P.D.,Shapiro, L.,DeKosky, B.J.
Antibody screening at reduced pH enables preferential selection of potently neutralizing antibodies targeting SARS-CoV-2.
Aiche J, 67:e17440-e17440, 2021
Cited by
PubMed Abstract: Antiviral monoclonal antibody (mAb) discovery enables the development of antibody-based antiviral therapeutics. Traditional antiviral mAb discovery relies on affinity between antibody and a viral antigen to discover potent neutralizing antibodies, but these approaches are inefficient because many high affinity mAbs have no neutralizing activity. We sought to determine whether screening for anti-SARS-CoV-2 mAbs at reduced pH could provide more efficient neutralizing antibody discovery. We mined the antibody response of a convalescent COVID-19 patient at both physiological pH (7.4) and reduced pH (4.5), revealing that SARS-CoV-2 neutralizing antibodies were preferentially enriched in pH 4.5 yeast display sorts. Structural analysis revealed that a potent new antibody called LP5 targets the SARS-CoV-2 N-terminal domain supersite via a unique binding recognition mode. Our data combine with evidence from prior studies to support antibody screening at pH 4.5 to accelerate antiviral neutralizing antibody discovery.
PubMed: 34898670
DOI: 10.1002/aic.17440
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (4.46 Å)
Structure validation

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