9LBS

Cryo-EM structure of Omicron BA.1 RBD complexed with ConBA-998,S309 and S304Fabs

Summary for 9LBS

• Entry DOI: 10.2210/pdb9lbs/pdb
• EMDB information: 62955
• Descriptor: Heavy chain of S309 Fab, Light chain of S309 Fab, Heavy chain of S304 Fab, ... (8 entities in total)
• Functional Keywords: omicron ba.1 rbd, conba-998 fab, s304 fab, s309 fab, viral protein/immune system, viral protein-immune system complex
• Biological source: Homo sapiens; More
• Total number of polymer chains: 7
• Total formula weight: 95572.84

Authors

Zhang, Z.,Ju, B.,Liu, C. (deposition date: 2025-01-03, release date: 2025-04-02, Last modification date: 2025-10-22)

Primary citation

Fan, Q.,Liu, C.,Guo, H.,Tang, S.,Wang, H.,Zhou, B.,Sun, Y.,Wang, M.,Ge, X.,Liu, L.,Ju, B.,Zhang, Z.
A distinctive IGHV3-66 SARS-CoV-2 neutralizing antibody elicited by primary infection with an Omicron variant.
Structure, 33:1165-1177.e6, 2025

PubMed Abstract: SARS-CoV-2 Omicron sub-variants continuously evolve under the pressure of neutralizing antibodies (nAbs), eliminating numerous potential elite monoclonal nAbs. The IGHV3-53/3-66 public nAbs have great potential for neutralizing SARS-CoV-2. However, it has been unclear whether a primary Omicron infection could also induce IGHV3-53/3-66 nAbs. In this study, we report an IGHV3-66-encoding monoclonal nAb, ConBA-998, that was elicited by primary infection with BA.1. ConBA-998 is an Omicron-dependent nAb with high binding affinity that triggers the shedding of the S1 subunit from the spike protein. The cryo-electron microscopy (cryo-EM) structure revealed the interactions between ConBA-998 and the Omicron BA.1 spike protein. ConBA-998 has a distinctive binding mode to receptor-binding domain (RBD) that differs from canonical IGHV3-53/3-66 nAbs. Overall, our findings indicate that Omicron may elicit unique specific nAbs distinct from those induced by pre-Omicron variants, providing further insights into SARS-CoV-2 variant-specific antibody responses.

PubMed: 40306272
DOI: 10.1016/j.str.2025.04.005

Experimental method

ELECTRON MICROSCOPY (3.41 Å)