8SDF

Crystal structure of SARS-CoV-2 receptor binding domain in complex with neutralizing antibody CC25.4

Summary for 8SDF

• Entry DOI: 10.2210/pdb8sdf/pdb
• Descriptor: Spike protein S1, Neutralizing antibody CC25.4 heavy chain, Neutralizing antibody CC25.4 light chain, ... (7 entities in total)
• Functional Keywords: sars-cov-2, coronavirus, antibody, immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 6
• Total formula weight: 143805.34

Authors

Yuan, M.,Wilson, I.A. (deposition date: 2023-04-06, release date: 2024-03-13, Last modification date: 2024-12-25)

Primary citation

Song, G.,Yuan, M.,Liu, H.,Capozzola, T.,Lin, R.N.,Torres, J.L.,He, W.T.,Musharrafieh, R.,Dueker, K.,Zhou, P.,Callaghan, S.,Mishra, N.,Yong, P.,Anzanello, F.,Avillion, G.,Vo, A.L.,Li, X.,Makhdoomi, M.,Feng, Z.,Zhu, X.,Peng, L.,Nemazee, D.,Safonova, Y.,Briney, B.,Ward, A.B.,Burton, D.R.,Wilson, I.A.,Andrabi, R.
Broadly neutralizing antibodies targeting a conserved silent face of spike RBD resist extreme SARS-CoV-2 antigenic drift.
Biorxiv, 2023

PubMed Abstract: Developing broad coronavirus vaccines requires identifying and understanding the molecular basis of broadly neutralizing antibody (bnAb) spike sites. In our previous work, we identified sarbecovirus spike RBD group 1 and 2 bnAbs. We have now shown that many of these bnAbs can still neutralize highly mutated SARS-CoV-2 variants, including the XBB.1.5. Structural studies revealed that group 1 bnAbs use recurrent germline-encoded CDRH3 features to interact with a conserved RBD region that overlaps with class 4 bnAb site. Group 2 bnAbs recognize a less well-characterized "site V" on the RBD and destabilize spike trimer. The site V has remained largely unchanged in SARS-CoV-2 variants and is highly conserved across diverse sarbecoviruses, making it a promising target for broad coronavirus vaccine development. Our findings suggest that targeted vaccine strategies may be needed to induce effective B cell responses to escape resistant subdominant spike RBD bnAb sites.

PubMed: 37162858
DOI: 10.1101/2023.04.26.538488

Experimental method

X-RAY DIFFRACTION (1.79 Å)