4UIH

Cryo-EM structure of Dengue virus serotype 2 strain New Guinea-C complexed with human antibody 2D22 Fab at 37 degree C. The Fab molecules were added to the virus before 37 degree C incubation.

Summary for 4UIH

• Entry DOI: 10.2210/pdb4uih/pdb
• Related: 4UIF
• EMDB information: 2968
• Descriptor: DENGUE VIRUS SEROTYPE 2 STRAIN NEW GUINEA-C E PROTEIN ECTODOMAIN, ANTIGEN-BINDING FRAGMENT OF HUMAN ANTIBODY 2D22 -HEAVY CHAIN, ANTIGEN-BINDING FRAGMENT OF HUMAN ANTIBODY 2D22 -LIGHT CHAIN (3 entities in total)
• Functional Keywords: viral protein, dengue virus, dengue serotype 2, human antibody, cryo-em, neutralization
• Biological source: DENGUE VIRUS 2 (ASIAN TIGER MOSQUITO); More
• Cellular location: Capsid protein C: Virion . Peptide pr: Secreted . Small envelope protein M: Virion membrane ; Multi-pass membrane protein . Envelope protein E: Virion membrane ; Multi-pass membrane protein . Non-structural protein 1: Secreted . Non-structural protein 2A: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Serine protease subunit NS2B: Host endoplasmic reticulum membrane; Multi-pass membrane protein . Serine protease NS3: Host endoplasmic reticulum membrane ; Peripheral membrane protein ; Cytoplasmic side . Non-structural protein 4A: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Non-structural protein 4B: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . RNA-directed RNA polymerase NS5: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side: P14340
• Total number of polymer chains: 7
• Total formula weight: 214882.73

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, J.E.,Lok, S.-M. (deposition date: 2015-03-30, 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 (20 Å)