6ZFO

Association of two complexes of largely structurally disordered Spike ectodomain with bound EY6A Fab

Summary for 6ZFO

• Entry DOI: 10.2210/pdb6zfo/pdb
• Related: 6ZCZ 6ZDG 6ZER 6ZHD
• EMDB information: 11184
• Descriptor: Spike protein S1, EY6A heavy chain, EY6A light chain, ... (4 entities in total)
• Functional Keywords: ey6a, rbd, spike glycoprotein, sars-cov-2, human neutralizing antibody, viral protein, immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 6
• Total formula weight: 139319.43

Authors

Duyvesteyn, H.M.E.,Zhou, D.,Zhao, Y.,Fry, E.E.,Ren, J.,Stuart, D.I. (deposition date: 2020-06-17, release date: 2020-07-08, Last modification date: 2021-12-22)

Primary citation

Zhou, D.,Duyvesteyn, H.M.E.,Chen, C.P.,Huang, C.G.,Chen, T.H.,Shih, S.R.,Lin, Y.C.,Cheng, C.Y.,Cheng, S.H.,Huang, Y.C.,Lin, T.Y.,Ma, C.,Huo, J.,Carrique, L.,Malinauskas, T.,Ruza, R.R.,Shah, P.N.M.,Tan, T.K.,Rijal, P.,Donat, R.F.,Godwin, K.,Buttigieg, K.R.,Tree, J.A.,Radecke, J.,Paterson, N.G.,Supasa, P.,Mongkolsapaya, J.,Screaton, G.R.,Carroll, M.W.,Gilbert-Jaramillo, J.,Knight, M.L.,James, W.,Owens, R.J.,Naismith, J.H.,Townsend, A.R.,Fry, E.E.,Zhao, Y.,Ren, J.,Stuart, D.I.,Huang, K.A.
Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient.
Nat.Struct.Mol.Biol., 27:950-958, 2020

PubMed Abstract: The COVID-19 pandemic has had an unprecedented health and economic impact and there are currently no approved therapies. We have isolated an antibody, EY6A, from an individual convalescing from COVID-19 and have shown that it neutralizes SARS-CoV-2 and cross-reacts with SARS-CoV-1. EY6A Fab binds the receptor binding domain (RBD) of the viral spike glycoprotein tightly (K of 2 nM), and a 2.6-Å-resolution crystal structure of an RBD-EY6A Fab complex identifies the highly conserved epitope, away from the ACE2 receptor binding site. Residues within this footprint are key to stabilizing the pre-fusion spike. Cryo-EM analyses of the pre-fusion spike incubated with EY6A Fab reveal a complex of the intact spike trimer with three Fabs bound and two further multimeric forms comprising the destabilized spike attached to Fab. EY6A binds what is probably a major neutralizing epitope, making it a candidate therapeutic for COVID-19.

PubMed: 32737466
DOI: 10.1038/s41594-020-0480-y

Experimental method

ELECTRON MICROSCOPY (4.4 Å)