4ZPV

Structure of MERS-Coronavirus Spike Receptor-binding Domain (England1 Strain) in Complex with Vaccine-Elicited Murine Neutralizing Antibody D12 (Crystal Form 2)

Summary for 4ZPV

• Entry DOI: 10.2210/pdb4zpv/pdb
• Related: 4ZPT 4ZPW
• Descriptor: D12 Fab Heavy chain, D12 Fab light chain, Spike glycoprotein, ... (4 entities in total)
• Functional Keywords: vaccine, immunogen, viral protein-immune system complex, viral protein/immune system
• Biological source: Human coronavirus EMC (isolate United Kingdom/H123990006/2012) (HCoV-EMC); More
• Cellular location: Spike protein S2: Virion membrane ; Single-pass type I membrane protein . Spike protein S1: Virion membrane ; Peripheral membrane protein : K9N5Q8
• Total number of polymer chains: 6
• Total formula weight: 140092.24

Authors

Joyce, M.G.,Mascola, J.R.,Graham, B.S.,Kwong, P.D. (deposition date: 2015-05-08, release date: 2015-10-21, Last modification date: 2020-07-29)

Primary citation

Wang, L.,Shi, W.,Joyce, M.G.,Modjarrad, K.,Zhang, Y.,Leung, K.,Lees, C.R.,Zhou, T.,Yassine, H.M.,Kanekiyo, M.,Yang, Z.Y.,Chen, X.,Becker, M.M.,Freeman, M.,Vogel, L.,Johnson, J.C.,Olinger, G.,Todd, J.P.,Bagci, U.,Solomon, J.,Mollura, D.J.,Hensley, L.,Jahrling, P.,Denison, M.R.,Rao, S.S.,Subbarao, K.,Kwong, P.D.,Mascola, J.R.,Kong, W.P.,Graham, B.S.
Evaluation of candidate vaccine approaches for MERS-CoV.
Nat Commun, 6:7712-7712, 2015

PubMed Abstract: The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanisms were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development.

PubMed: 26218507
DOI: 10.1038/ncomms8712

Experimental method

X-RAY DIFFRACTION (3.2 Å)