7uzc

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Structure of the SARS-CoV-2 RBD in complex with the mouse antibody Fab fragment, M8a-34

Structural highlights

7uzc is a 6 chain structure with sequence from Mus musculus and Severe acute respiratory syndrome coronavirus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.2Å
Ligands:BMA, MAN, NAG
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

Increased immune evasion by SARS-CoV-2 variants of concern highlights the need for new therapeutic neutralizing antibodies. Immunization with nanoparticles co-displaying spike receptor-binding domains (RBDs) from eight sarbecoviruses (mosaic-8 RBD-nanoparticles) efficiently elicits cross-reactive polyclonal antibodies against conserved sarbecovirus RBD epitopes. Here, we identified monoclonal antibodies (mAbs) capable of cross-reactive binding and neutralization of animal sarbecoviruses and SARS-CoV-2 variants by screening single mouse B cells secreting IgGs that bind two or more sarbecovirus RBDs. Single-particle cryo-EM structures of antibody-spike complexes, including a Fab-Omicron complex, mapped neutralizing mAbs to conserved class 1/4 RBD epitopes. Structural analyses revealed neutralization mechanisms, potentials for intra-spike trimer cross-linking by IgGs, and induced changes in trimer upon Fab binding. In addition, we identified a mAb-resembling Bebtelovimab, an EUA-approved human class 3 anti-RBD mAb. These results support using mosaic RBD-nanoparticle vaccination to generate and identify therapeutic pan-sarbecovirus and pan-variant mAbs.

Neutralizing monoclonal antibodies elicited by mosaic RBD nanoparticles bind conserved sarbecovirus epitopes.,Fan C, Cohen AA, Park M, Hung AF, Keeffe JR, Gnanapragasam PNP, Lee YE, Gao H, Kakutani LM, Wu Z, Kleanthous H, Malecek KE, Williams JC, Bjorkman PJ Immunity. 2022 Dec 13;55(12):2419-2435.e10. doi: 10.1016/j.immuni.2022.10.019. , Epub 2022 Oct 27. PMID:36370711[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
4 reviews cite this structure
Musunuri et al. (2024)
No citations found

See Also

References

  1. Fan C, Cohen AA, Park M, Hung AF, Keeffe JR, Gnanapragasam PNP, Lee YE, Gao H, Kakutani LM, Wu Z, Kleanthous H, Malecek KE, Williams JC, Bjorkman PJ. Neutralizing monoclonal antibodies elicited by mosaic RBD nanoparticles bind conserved sarbecovirus epitopes. Immunity. 2022 Dec 13;55(12):2419-2435.e10. doi: 10.1016/j.immuni.2022.10.019. , Epub 2022 Oct 27. PMID:36370711 doi:http://dx.doi.org/10.1016/j.immuni.2022.10.019

Contents


PDB ID 7uzc

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