5YY5

Structural definition of a unique neutralization epitope on the receptor-binding domain of MERS-CoV spike glycoprotein

Summary for 5YY5

• Entry DOI: 10.2210/pdb5yy5/pdb
• Descriptor: MERS-CoV RBD, Heavy chain, Light chain, ... (6 entities in total)
• Functional Keywords: mers-cov, spike glycorptotein, neutralizing antibody, viral protein
• Biological source: Middle East respiratory syndrome coronavirus; More
• Total number of polymer chains: 6
• Total formula weight: 93868.56

Authors

Zhang, S.,Wang, P.,Zhou, P.,Wang, X.,Zhang, L. (deposition date: 2017-12-08, release date: 2018-08-01, Last modification date: 2020-07-29)

Primary citation

Zhang, S.,Zhou, P.,Wang, P.,Li, Y.,Jiang, L.,Jia, W.,Wang, H.,Fan, A.,Wang, D.,Shi, X.,Fang, X.,Hammel, M.,Wang, S.,Wang, X.,Zhang, L.
Structural Definition of a Unique Neutralization Epitope on the Receptor-Binding Domain of MERS-CoV Spike Glycoprotein
Cell Rep, 24:441-452, 2018

PubMed Abstract: The major mechanism of antibody-mediated neutralization of the Middle East respiratory syndrome coronavirus (MERS-CoV) involves competition with the cellular receptor dipeptidyl peptidase 4 (DPP4) for binding to the receptor-binding domain (RBD) of the spike (S) glycoprotein. Here, we report a unique epitope and unusual neutralizing mechanism of the isolated human antibody MERS-4. Structurally, MERS-4 approached the RBD from the outside of the RBD-DPP4 binding interface. Such binding resulted in the folding of the β5-β6 loop toward a shallow groove on the RBD interface critical for accommodating DPP4. The key residues for binding are identified through site-directed mutagenesis. Structural modeling revealed that MERS-4 binds to RBD only in the "up" position in the S trimer. Furthermore, MERS-4 demonstrated synergy with several reported antibodies. These results indicate that MERS-4 neutralizes MERS-CoV by indirect rather than direct competition with DPP4. This mechanism provides a valuable addition for the combined use of antibodies against MERS-CoV infection.

PubMed: 29996104
DOI: 10.1016/j.celrep.2018.06.041

Experimental method

X-RAY DIFFRACTION (2.8 Å)