5VIC

Crystal structure of anti-Zika antibody Z004 bound to DENV-1 Envelope protein DIII

Summary for 5VIC

• Entry DOI: 10.2210/pdb5vic/pdb
• Related: 5vig
• Descriptor: Fab heavy chain, Fab light chain, Dengue 1 Envelope DIII domain (3 entities in total)
• Functional Keywords: antibody, fab, zika, dengue, recurrent, neutralizing, immune system
• Biological source: Homo sapiens (Human); More
• Cellular location: Secreted : P0DOX7; 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-alpha: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Non-structural protein 2A: Host endoplasmic reticulum membrane ; Multi- pass membrane protein . Serine protease subunit NS2B: Host endoplasmic reticulum membrane ; Peripheral membrane protein ; Cytoplasmic side . 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: 3
• Total formula weight: 59327.35

Authors

Keeffe, J.R.,West Jr., A.P.,Gristick, H.B.,Bjorkman, P.J. (deposition date: 2017-04-14, release date: 2017-05-03, Last modification date: 2024-10-09)

Primary citation

Robbiani, D.F.,Bozzacco, L.,Keeffe, J.R.,Khouri, R.,Olsen, P.C.,Gazumyan, A.,Schaefer-Babajew, D.,Avila-Rios, S.,Nogueira, L.,Patel, R.,Azzopardi, S.A.,Uhl, L.F.K.,Saeed, M.,Sevilla-Reyes, E.E.,Agudelo, M.,Yao, K.H.,Golijanin, J.,Gristick, H.B.,Lee, Y.E.,Hurley, A.,Caskey, M.,Pai, J.,Oliveira, T.,Wunder, E.A.,Sacramento, G.,Nery, N.,Orge, C.,Costa, F.,Reis, M.G.,Thomas, N.M.,Eisenreich, T.,Weinberger, D.M.,de Almeida, A.R.P.,West, A.P.,Rice, C.M.,Bjorkman, P.J.,Reyes-Teran, G.,Ko, A.I.,MacDonald, M.R.,Nussenzweig, M.C.
Recurrent Potent Human Neutralizing Antibodies to Zika Virus in Brazil and Mexico.
Cell, 169:597-609.e11, 2017

PubMed Abstract: Antibodies to Zika virus (ZIKV) can be protective. To examine the antibody response in individuals who develop high titers of anti-ZIKV antibodies, we screened cohorts in Brazil and Mexico for ZIKV envelope domain III (ZEDIII) binding and neutralization. We find that serologic reactivity to dengue 1 virus (DENV1) EDIII before ZIKV exposure is associated with increased ZIKV neutralizing titers after exposure. Antibody cloning shows that donors with high ZIKV neutralizing antibody titers have expanded clones of memory B cells that express the same immunoglobulin VH3-23/VK1-5 genes. These recurring antibodies cross-react with DENV1, but not other flaviviruses, neutralize both DENV1 and ZIKV, and protect mice against ZIKV challenge. Structural analyses reveal the mechanism of recognition of the ZEDIII lateral ridge by VH3-23/VK1-5 antibodies. Serologic testing shows that antibodies to this region correlate with serum neutralizing activity to ZIKV. Thus, high neutralizing responses to ZIKV are associated with pre-existing reactivity to DENV1 in humans.

PubMed: 28475892
DOI: 10.1016/j.cell.2017.04.024

Experimental method

X-RAY DIFFRACTION (3 Å)