6PZ8

MERS S0 trimer in complex with variable domain of antibody G2

Summary for 6PZ8

• Entry DOI: 10.2210/pdb6pz8/pdb
• EMDB information: 20527
• Descriptor: S protein, G2 heavy chain, G2 light chain, ... (8 entities in total)
• Functional Keywords: mers-cov, coronavirus, dpp4, receptor-binding, membrane fusion, viral protein-immune system complex, viral protein/immune system
• Biological source: Middle East respiratory syndrome-related coronavirus; More
• Total number of polymer chains: 12
• Total formula weight: 555654.29

Authors

Bowman, C.A.,Pallesen, J.,Ward, A.B. (deposition date: 2019-07-31, release date: 2019-10-09, Last modification date: 2024-11-06)

Primary citation

Wang, N.,Rosen, O.,Wang, L.,Turner, H.L.,Stevens, L.J.,Corbett, K.S.,Bowman, C.A.,Pallesen, J.,Shi, W.,Zhang, Y.,Leung, K.,Kirchdoerfer, R.N.,Becker, M.M.,Denison, M.R.,Chappell, J.D.,Ward, A.B.,Graham, B.S.,McLellan, J.S.
Structural Definition of a Neutralization-Sensitive Epitope on the MERS-CoV S1-NTD.
Cell Rep, 28:3395-3405.e6, 2019

PubMed Abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) emerged into the human population in 2012 and has caused substantial morbidity and mortality. Potently neutralizing antibodies targeting the receptor-binding domain (RBD) on MERS-CoV spike (S) protein have been characterized, but much less is known about antibodies targeting non-RBD epitopes. Here, we report the structural and functional characterization of G2, a neutralizing antibody targeting the MERS-CoV S1 N-terminal domain (S1-NTD). Structures of G2 alone and in complex with the MERS-CoV S1-NTD define a site of vulnerability comprising two loops, each of which contain a residue mutated in G2-escape variants. Cell-surface binding studies and in vitro competition experiments demonstrate that G2 strongly disrupts the attachment of MERS-CoV S to its receptor, dipeptidyl peptidase-4 (DPP4), with the inhibition requiring the native trimeric S conformation. These results advance our understanding of antibody-mediated neutralization of coronaviruses and should facilitate the development of immunotherapeutics and vaccines against MERS-CoV.

PubMed: 31553909
DOI: 10.1016/j.celrep.2019.08.052

Experimental method

ELECTRON MICROSCOPY (4.19 Å)