4FFZ

Crystal Structure of DENV1-E111 fab fragment bound to DENV-1 DIII (Western Pacific-74 strain).

Summary for 4FFZ

• Entry DOI: 10.2210/pdb4ffz/pdb
• Related: 3IRC 4FFZ
• Descriptor: Envelope protein E, DENV1-E111 fab fragment (light chain), DENV1-E111 fab fragment (heavy chain) (3 entities in total)
• Functional Keywords: structural genomics, antibody fab fragment, flavivirus, dengue virus, niaid, national institute of allergy and infectious diseases, center for structural genomics of infectious diseases, csgid, immunoglobulin-like domain, viral envelope protein, virion, immune system, immune system-viral protein complex, immune system/viral protein
• Biological source: Dengue virus 1 (DENV-1); 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 : P17763
• Total number of polymer chains: 6
• Total formula weight: 119059.06

Authors

Austin, S.K.,Nelson, C.A.,Fremont, D.H.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2012-06-01, release date: 2012-06-27, Last modification date: 2024-11-20)

Primary citation

Austin, S.K.,Dowd, K.A.,Shrestha, B.,Nelson, C.A.,Edeling, M.A.,Johnson, S.,Pierson, T.C.,Diamond, M.S.,Fremont, D.H.
Structural Basis of Differential Neutralization of DENV-1 Genotypes by an Antibody that Recognizes a Cryptic Epitope.
Plos Pathog., 8:e1002930-e1002930, 2012

PubMed Abstract: We previously developed a panel of neutralizing monoclonal antibodies against Dengue virus (DENV)-1, of which few exhibited inhibitory activity against all DENV-1 genotypes. This finding is consistent with reports observing variable neutralization of different DENV strains and genotypes using serum from individuals that experienced natural infection or immunization. Herein, we describe the crystal structures of DENV1-E111 bound to a novel CC' loop epitope on domain III (DIII) of the E protein from two different DENV-1 genotypes. Docking of our structure onto the available cryo-electron microscopy models of DENV virions revealed that the DENV1-E111 epitope was inaccessible, suggesting that this antibody recognizes an uncharacterized virus conformation. While the affinity of binding between DENV1-E111 and DIII varied by genotype, we observed limited correlation with inhibitory activity. Instead, our results support the conclusion that potent neutralization depends on genotype-dependent exposure of the CC' loop epitope. These findings establish new structural complexity of the DENV virion, which may be relevant for the choice of DENV strain for induction or analysis of neutralizing antibodies in the context of vaccine development.

PubMed: 23055922
DOI: 10.1371/journal.ppat.1002930

Experimental method

X-RAY DIFFRACTION (3.8 Å)