7MXP
Cryo-EM structure of NTD-directed neutralizing antibody LP5 Fab in complex with SARS-CoV-2 S2P spike
Summary for 7MXP
Entry DOI | 10.2210/pdb7mxp/pdb |
EMDB information | 24075 |
Descriptor | Spike glycoprotein, LP5 Fab Heavy Chain, LP5 Fab Light Chain, ... (7 entities in total) |
Functional Keywords | neturalsing antibody, fusion protein, spike glycoprotein, nrd, ntd-directed antibody, lp5, viral protein, immune system, viral protein-immune system complex, viral protein/immune system |
Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2) More |
Total number of polymer chains | 9 |
Total formula weight | 513955.83 |
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 citation | Madan, 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: 34898670DOI: 10.1002/aic.17440 PDB entries with the same primary citation |
Experimental method | ELECTRON MICROSCOPY (4.46 Å) |
Structure validation
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