7N3H

Crystal structure of an anti-SARS-CoV-2 human neutralizing antibody Fab fragment C099

Summary for 7N3H

• Entry DOI: 10.2210/pdb7n3h/pdb
• Descriptor: C099 Fab Heavy Chain, C099 Fab Light Chain (3 entities in total)
• Functional Keywords: severe acute respiratory syndrome coronavirus-2, spike protein, neutralizing antibodies, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 47702.18

Authors

Flyak, A.I.,Bjorkman, P.J.,Barnes, C.O. (deposition date: 2021-06-01, release date: 2021-08-04, Last modification date: 2024-10-30)

Primary citation

Muecksch, F.,Weisblum, Y.,Barnes, C.O.,Schmidt, F.,Schaefer-Babajew, D.,Wang, Z.,C Lorenzi, J.C.,Flyak, A.I.,DeLaitsch, A.T.,Huey-Tubman, K.E.,Hou, S.,Schiffer, C.A.,Gaebler, C.,Da Silva, J.,Poston, D.,Finkin, S.,Cho, A.,Cipolla, M.,Oliveira, T.Y.,Millard, K.G.,Ramos, V.,Gazumyan, A.,Rutkowska, M.,Caskey, M.,Nussenzweig, M.C.,Bjorkman, P.J.,Hatziioannou, T.,Bieniasz, P.D.
Affinity maturation of SARS-CoV-2 neutralizing antibodies confers potency, breadth, and resilience to viral escape mutations.
Immunity, 54:1853-, 2021

PubMed Abstract: Antibodies elicited by infection accumulate somatic mutations in germinal centers that can increase affinity for cognate antigens. We analyzed 6 independent groups of clonally related severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) Spike receptor-binding domain (RBD)-specific antibodies from 5 individuals shortly after infection and later in convalescence to determine the impact of maturation over months. In addition to increased affinity and neutralization potency, antibody evolution changed the mutational pathways for the acquisition of viral resistance and restricted neutralization escape options. For some antibodies, maturation imposed a requirement for multiple substitutions to enable escape. For certain antibodies, affinity maturation enabled the neutralization of circulating SARS-CoV-2 variants of concern and heterologous sarbecoviruses. Antibody-antigen structures revealed that these properties resulted from substitutions that allowed additional variability at the interface with the RBD. These findings suggest that increasing antibody diversity through prolonged or repeated antigen exposure may improve protection against diversifying SARS-CoV-2 populations, and perhaps against other pandemic threat coronaviruses.

PubMed: 34331873
DOI: 10.1016/j.immuni.2021.07.008

Experimental method

X-RAY DIFFRACTION (1.26 Å)