8DGX

Crystal structure of MERS-CoV spike stem helix peptide in complex with Fab of broadly neutralizing antibody CC68.109 isolated from a vaccinated COVID-19 convalescent

Summary for 8DGX

• Entry DOI: 10.2210/pdb8dgx/pdb
• Descriptor: Antibody CC68.109 Fab heavy chain, Antibody CC68.109 Fab light chain, Spike protein S2' (3 entities in total)
• Functional Keywords: broadly neutralizing antibody, pan-betacoronavirus, s2 stem helix, spike, sars-cov-2, mers-cov, hcov-hku1, sarbecovirus, cross-reactive, cross-neutralizing, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 100922.25

Authors

Liu, H.,Wilson, I.A. (deposition date: 2022-06-24, release date: 2023-01-25, Last modification date: 2023-10-25)

Primary citation

Zhou, P.,Song, G.,Liu, H.,Yuan, M.,He, W.T.,Beutler, N.,Zhu, X.,Tse, L.V.,Martinez, D.R.,Schafer, A.,Anzanello, F.,Yong, P.,Peng, L.,Dueker, K.,Musharrafieh, R.,Callaghan, S.,Capozzola, T.,Limbo, O.,Parren, M.,Garcia, E.,Rawlings, S.A.,Smith, D.M.,Nemazee, D.,Jardine, J.G.,Safonova, Y.,Briney, B.,Rogers, T.F.,Wilson, I.A.,Baric, R.S.,Gralinski, L.E.,Burton, D.R.,Andrabi, R.
Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease.
Immunity, 56:669-686.e7, 2023

PubMed Abstract: Pan-betacoronavirus neutralizing antibodies may hold the key to developing broadly protective vaccines against novel pandemic coronaviruses and to more effectively respond to SARS-CoV-2 variants. The emergence of Omicron and subvariants of SARS-CoV-2 illustrates the limitations of solely targeting the receptor-binding domain (RBD) of the spike (S) protein. Here, we isolated a large panel of broadly neutralizing antibodies (bnAbs) from SARS-CoV-2 recovered-vaccinated donors, which targets a conserved S2 region in the betacoronavirus spike fusion machinery. Select bnAbs showed broad in vivo protection against all three deadly betacoronaviruses, SARS-CoV-1, SARS-CoV-2, and MERS-CoV, which have spilled over into humans in the past two decades. Structural studies of these bnAbs delineated the molecular basis for their broad reactivity and revealed common antibody features targetable by broad vaccination strategies. These bnAbs provide new insights and opportunities for antibody-based interventions and for developing pan-betacoronavirus vaccines.

PubMed: 36889306
DOI: 10.1016/j.immuni.2023.02.005

Experimental method

X-RAY DIFFRACTION (2.89 Å)