5W9K

MERS S ectodomain trimer in complex with variable domain of neutralizing antibody G4

Summary for 5W9K

• Entry DOI: 10.2210/pdb5w9k/pdb
• EMDB information: 8783 8784 8785 8786 8787 8788 8789 8790 8791 8792 8793
• Descriptor: Spike glycoprotein, G4 VH, G4 VL (3 entities in total)
• Functional Keywords: immunogen, peplomer, viral spike, mers, mers s protein, antibody, g4, viral protein
• Biological source: Middle East respiratory syndrome-related coronavirus; More
• Total number of polymer chains: 12
• Total formula weight: 1025494.97

Authors

Pallesen, J.,Ward, A.B. (deposition date: 2017-06-23, release date: 2017-08-16, Last modification date: 2024-10-23)

Primary citation

Pallesen, J.,Wang, N.,Corbett, K.S.,Wrapp, D.,Kirchdoerfer, R.N.,Turner, H.L.,Cottrell, C.A.,Becker, M.M.,Wang, L.,Shi, W.,Kong, W.P.,Andres, E.L.,Kettenbach, A.N.,Denison, M.R.,Chappell, J.D.,Graham, B.S.,Ward, A.B.,McLellan, J.S.
Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen.
Proc. Natl. Acad. Sci. U.S.A., 114:E7348-E7357, 2017

PubMed Abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) is a lineage C betacoronavirus that since its emergence in 2012 has caused outbreaks in human populations with case-fatality rates of ∼36%. As in other coronaviruses, the spike (S) glycoprotein of MERS-CoV mediates receptor recognition and membrane fusion and is the primary target of the humoral immune response during infection. Here we use structure-based design to develop a generalizable strategy for retaining coronavirus S proteins in the antigenically optimal prefusion conformation and demonstrate that our engineered immunogen is able to elicit high neutralizing antibody titers against MERS-CoV. We also determined high-resolution structures of the trimeric MERS-CoV S ectodomain in complex with G4, a stem-directed neutralizing antibody. The structures reveal that G4 recognizes a glycosylated loop that is variable among coronaviruses and they define four conformational states of the trimer wherein each receptor-binding domain is either tightly packed at the membrane-distal apex or rotated into a receptor-accessible conformation. Our studies suggest a potential mechanism for fusion initiation through sequential receptor-binding events and provide a foundation for the structure-based design of coronavirus vaccines.

PubMed: 28807998
DOI: 10.1073/pnas.1707304114

Experimental method

ELECTRON MICROSCOPY (4.6 Å)