6PXG

Crystal Structure of MERS-CoV neutralizing antibody G2 Fab

Summary for 6PXG

• Entry DOI: 10.2210/pdb6pxg/pdb
• Descriptor: G2 Fab Heavy Chain, G2 Fab Light chain (3 entities in total)
• Functional Keywords: immune system, antibody, fusion glycoprotein
• Biological source: Mus musculus; More
• Total number of polymer chains: 8
• Total formula weight: 192545.41

Authors

Wang, N.,McLellan, J.S. (deposition date: 2019-07-26, release date: 2019-09-25, Last modification date: 2019-12-18)

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

X-RAY DIFFRACTION (2.1 Å)