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. 2019 Jun 6;8(1):841–856. doi: 10.1080/22221751.2019.1624482

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© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Figure 4. — Advancement in structural studies of MERS-CoV neutralizing monoclonal antibodies. (A) Structure of MERS-CoV spike trimer ectodomain (PDB ID: 5X5F). A single protomer of the trimeric spike protein with RBD in ‘up' conformation is shown as molecular surface. The RBD, NTD and S2 subunit are coloured in green, paleyellow and lightblue, respectively. The two remaining protomers with RBD in ‘down' conformation are shown in cartoon representation and coloured in wheat. (B) Structures of MERS-CoV neutralizing antibodies targeting RBD. Antibodies are classified into three groups and shown as cartoon representation. The RBD is coloured in green and antibodies in different colours. Group 1 includes MERS-27 (PDB ID: 4ZS6), D12 (PDB ID: 4ZPT), 4C2 (PDB ID: 5DO2) and JC57-14 (PDB ID: 6C6Y). Group 2 includes m336 (PDB ID: 4XAK), MCA1 (PDB ID: 5GMQ), CDC2-C2 (PDB ID: 6C6Z) and MERS-GD27. Group 3 includes MERS-4 (PDB ID: 5ZXV) and MERS-4V2 (PDB ID: 5YY5). (C) Neutralizing mechanisms of MERS-CoV neutralizing antibodies targeting RBD. The left panel shows the structural superimposition of the representative antibodies from the three groups (MERS-27, m336 and MERS-4) and DPP4 (coloured in yellow) bound to RBD (coloured in green, PDB ID: 4L72) at the same time. The right panel is enlarged view of steric clashes between the antibodies and the DPP4 and a significant conformational difference in the RBD β5-β6 loop between antibody-bound and DPP4-bound states. (D) Structure of G4 fab (coloured in teal) in complex with spike trimer (PDB ID: 5W9H). (E) Side views of spike monomer bound to G4 fab. The enlarged view of the glycosylated loop in the S2 subunit recognized by G4 is shown on the right.