8HEC

SARS-CoV-2 Spike trimer in complex with RmAb 9H1 Fab in the class 2 conformation

Summary for 8HEC

• Entry DOI: 10.2210/pdb8hec/pdb
• EMDB information: 34687
• Descriptor: Spike glycoprotein, rabbit antibody 9H1 light chain, rabbit antibody 9H1 heavy chain, ... (5 entities in total)
• Functional Keywords: viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 9
• Total formula weight: 487079.87

Authors

Guo, H.,Gao, Y.,Lu, Y.,Yang, H.,Ji, X. (deposition date: 2022-11-08, release date: 2023-04-26, Last modification date: 2024-11-06)

Primary citation

Chu, X.,Ding, X.,Yang, Y.,Lu, Y.,Li, T.,Gao, Y.,Zheng, L.,Xiao, H.,Yang, T.,Cheng, H.,Huang, H.,Liu, Y.,Lou, Y.,Wu, C.,Chen, Y.,Yang, H.,Ji, X.,Guo, H.
Mechanism of an RBM-targeted rabbit monoclonal antibody 9H1 neutralizing SARS-CoV-2.
Biochem.Biophys.Res.Commun., 660:43-49, 2023

PubMed Abstract: The COVID-19 pandemic, caused by SARS-CoV-2, has led to over 750 million infections and 6.8 million deaths worldwide since late 2019. Due to the continuous evolution of SARS-CoV-2, many significant variants have emerged, creating ongoing challenges to the prevention and treatment of the pandemic. Therefore, the study of antibody responses against SARS-CoV-2 is essential for the development of vaccines and therapeutics. Here we perform single particle cryo-electron microscopy (cryo-EM) structure determination of a rabbit monoclonal antibody (RmAb) 9H1 in complex with the SARS-CoV-2 wild-type (WT) spike trimer. Our structural analysis shows that 9H1 interacts with the receptor-binding motif (RBM) region of the receptor-binding domain (RBD) on the spike protein and by directly competing with angiotensin-converting enzyme 2 (ACE2), it blocks the binding of the virus to the receptor and achieves neutralization. Our findings suggest that utilizing rabbit-derived mAbs provides valuable insights into the molecular interactions between neutralizing antibodies and spike proteins and may also facilitate the development of therapeutic antibodies and expand the antibody library.

PubMed: 37062240
DOI: 10.1016/j.bbrc.2023.04.002

Experimental method

ELECTRON MICROSCOPY (3.5 Å)