4C2I

Cryo-EM structure of Dengue virus serotype 1 complexed with Fab fragments of human antibody 1F4

Summary for 4C2I

• Entry DOI: 10.2210/pdb4c2i/pdb
• EMDB information: 2442
• Related PRD ID: PRD_900017
• Descriptor: ENVELOPE PROTEIN, POLYPROTEIN, HEAVY CHAIN FAB FRAGMENT OF ANTIBODY 1F4, ... (7 entities in total)
• Functional Keywords: virus, e proteins, neutralization
• Biological source: DENGUE VIRUS 1; More
• Total number of polymer chains: 10
• Total formula weight: 289287.33

Authors

Fibriansah, G.,Tan, J.L.,de Alwis, R.,Smith, S.A.,Ng, T.-S.,Kostyuchenko, V.A.,Ibarra, K.D.,Harris, E.,de Silva, A.,Crowe Junior, J.E.,Lok, S.-M. (deposition date: 2013-08-18, release date: 2014-01-29, Last modification date: 2024-05-08)

Primary citation

Fibriansah, G.,Tan, J.L.,Smith, S.A.,De Alwis, A.R.,Ng, T.,Kostyuchenko, V.A.,Ibarra, K.D.,Wang, J.,Harris, E.,De Silva, A.,Crowe, J.E.J.,Lok, S.
A Potent Anti-Dengue Human Antibody Preferentially Recognizes the Conformation of E Protein Monomers Assembled on the Virus Surface.
Embo Mol.Med., 6:358-, 2014

PubMed Abstract: Dengue virus (DENV), which consists of four serotypes (DENV1-4), infects over 400 million people annually. Previous studies have indicated most human monoclonal antibodies (HMAbs) from dengue patients are cross-reactive and poorly neutralizing. Rare neutralizing HMAbs are usually serotype-specific and bind to quaternary structure-dependent epitopes. We determined the structure of DENV1 complexed with Fab fragments of a highly potent HMAb 1F4 to 6 Å resolution by cryo-EM. Although HMAb 1F4 appeared to bind to virus and not E proteins in ELISAs in the previous study, our structure showed that the epitope is located within an envelope (E) protein monomer, and not across neighboring E proteins. The Fab molecules bind to domain I (DI), and DI-DII hinge of the E protein. We also showed that HMAb 1F4 can neutralize DENV at different stages of viral entry in a cell type and receptor dependent manner. The structure reveals the mechanism by which this potent and specific antibody blocks viral infection.

PubMed: 24421336
DOI: 10.1002/EMMM.201303404

Experimental method

ELECTRON MICROSCOPY (6 Å)