5A1Z

Cryo-EM structure of Dengue virus serotype 2 strain PVP94-07 complexed with human antibody 2D22 Fab at 37 degrees C

Summary for 5A1Z

• Entry DOI: 10.2210/pdb5a1z/pdb
• EMDB information: 2996
• Descriptor: ENVELOPE PROTEIN, MEMBRANE GLYCOPROTEIN, ANTIGEN-BINDING FRAGMENT OF HUMAN ANTIBODY 2D22 - HEAVY CHAIN, ... (4 entities in total)
• Functional Keywords: virus, dengue virus, human antibody, cryo-em, neutralization
• Biological source: DENGUE VIRUS 2; More
• Cellular location: Host endoplasmic reticulum membrane ; Multi-pass membrane protein : G9FRP5
• Total number of polymer chains: 12
• Total formula weight: 264791.42

Authors

Fibriansah, G.,Ibarra, K.D.,Ng, T.S.,Smith, S.A.,Tan, J.L.,Lim, X.N.,Ooi, J.S.G.,Kostyuchenko, V.A.,Wang, J.,de Silva, A.M.,Harris, E.,Crowe Jr, J.E.,Lok, S.M. (deposition date: 2015-05-06, release date: 2015-07-15, Last modification date: 2024-05-08)

Primary citation

Fibriansah, G.,Ibarra, K.D.,Ng, T.S.,Smith, S.A.,Tan, J.L.,Lim, X.N.,Ooi, J.S.,Kostyuchenko, V.A.,Wang, J.,de Silva, A.M.,Harris, E.,Crowe, J.E.,Lok, S.M.
Cryo-EM structure of an antibody that neutralizes dengue virus type 2 by locking E protein dimers.
Science, 349:88-91, 2015

PubMed Abstract: There are four closely-related dengue virus (DENV) serotypes. Infection with one serotype generates antibodies that may cross-react and enhance infection with other serotypes in a secondary infection. We demonstrated that DENV serotype 2 (DENV2)-specific human monoclonal antibody (HMAb) 2D22 is therapeutic in a mouse model of antibody-enhanced severe dengue disease. We determined the cryo-electron microscopy (cryo-EM) structures of HMAb 2D22 complexed with two different DENV2 strains. HMAb 2D22 binds across viral envelope (E) proteins in the dimeric structure, which probably blocks the E protein reorganization required for virus fusion. HMAb 2D22 "locks" two-thirds of or all dimers on the virus surface, depending on the strain, but neutralizes these DENV2 strains with equal potency. The epitope defined by HMAb 2D22 is a potential target for vaccines and therapeutics.

PubMed: 26138979
DOI: 10.1126/science.aaa8651

Experimental method

ELECTRON MICROSCOPY (6.9 Å)