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| | ==Crystal structure of anti-Zika antibody Z004 bound to DENV-1 Envelope protein DIII== | | ==Crystal structure of anti-Zika antibody Z004 bound to DENV-1 Envelope protein DIII== |
| - | <StructureSection load='5vic' size='340' side='right' caption='[[5vic]], [[Resolution|resolution]] 3.00Å' scene=''> | + | <StructureSection load='5vic' size='340' side='right'caption='[[5vic]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5vic]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VIC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VIC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5vic]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Dengue_virus_1_Nauru/West_Pac/1974 Dengue virus 1 Nauru/West Pac/1974] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VIC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VIC FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vig|5vig]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5vic FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vic OCA], [http://pdbe.org/5vic PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vic RCSB], [http://www.ebi.ac.uk/pdbsum/5vic PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vic ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5vic FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vic OCA], [https://pdbe.org/5vic PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vic RCSB], [https://www.ebi.ac.uk/pdbsum/5vic PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vic ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/POLG_DEN1W POLG_DEN1W]] Capsid protein C self-assembles to form an icosahedral capsid about 30 nm in diameter. The capsid encapsulates the genomic RNA (By similarity). prM acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is matured in the last step of virion assembly, presumably to avoid catastrophic activation of the viral fusion peptide induced by the acidic pH of the trans-Golgi network. After cleavage by host furin, the pr peptide is released in the extracellular medium and small envelope protein M and envelope protein E homodimers are dissociated (By similarity). Envelope protein E binding to host cell surface receptor is followed by virus internalization through clathrin-mediated endocytosis. Envelope protein E is subsequently involved in membrane fusion between virion and host late endosomes. Synthesized as a homodimer with prM which acts as a chaperone for envelope protein E. After cleavage of prM, envelope protein E dissociate from small envelope protein M and homodimerizes (By similarity). Non-structural protein 1 is involved in virus replication and regulation of the innate immune response. Soluble and membrane-associated NS1 may activate human complement and induce host vascular leakage. This effect might explain the clinical manifestations of dengue hemorrhagic fever and dengue shock syndrome (By similarity). Non-structural protein 2A may be involved viral RNA replication and capsid assembly (Potential). Non-structural protein 2B is a required cofactor for the serine protease function of NS3 (By similarity). Serine protease NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS2B, performs its autocleavage and cleaves the polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and unwinds dsRNA in the 3' to 5' direction (By similarity). Non-structural protein 4A induces host endoplasmic reticulum membrane rearrangements leading to the formation of virus-induced membranous vesicles hosting the dsRNA and polymerase, functioning as a replication complex. NS4A might also regulate the ATPase activity of the NS3 helicase (By similarity). Peptide 2k functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter (By similarity). Non-structural protein 4B inhibits interferon (IFN)-induced host STAT1 phosphorylation and nuclear translocation, thereby preventing the establishment of cellular antiviral state by blocking the IFN-alpha/beta pathway (By similarity). RNA-directed RNA polymerase NS5 replicates the viral (+) and (-) genome, and performs the capping of genomes in the cytoplasm. NS5 methylates viral RNA cap at guanine N-7 and ribose 2'-O positions. Besides its role in genome replication, also prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) signaling pathway. Inhibits host TYK2 and STAT2 phosphorylation, thereby preventing activation of JAK-STAT signaling pathway (By similarity). | + | [https://www.uniprot.org/uniprot/S6B291_HUMAN S6B291_HUMAN] |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | 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. |
| | + | |
| | + | Recurrent Potent Human Neutralizing Antibodies to Zika Virus in Brazil and Mexico.,Robbiani DF, Bozzacco L, Keeffe JR, Khouri R, Olsen PC, Gazumyan A, Schaefer-Babajew D, Avila-Rios S, Nogueira L, Patel R, Azzopardi SA, Uhl LFK, Saeed M, Sevilla-Reyes EE, Agudelo M, Yao KH, Golijanin J, Gristick HB, Lee YE, Hurley A, Caskey M, Pai J, Oliveira T, Wunder EA Jr, Sacramento G, Nery N Jr, Orge C, Costa F, Reis MG, Thomas NM, Eisenreich T, Weinberger DM, de Almeida ARP, West AP Jr, Rice CM, Bjorkman PJ, Reyes-Teran G, Ko AI, MacDonald MR, Nussenzweig MC Cell. 2017 May 4;169(4):597-609.e11. doi: 10.1016/j.cell.2017.04.024. PMID:28475892<ref>PMID:28475892</ref> |
| | + | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 5vic" style="background-color:#fffaf0;"></div> |
| | + | == References == |
| | + | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bjorkman, P J]] | + | [[Category: Dengue virus 1 Nauru/West Pac/1974]] |
| - | [[Category: Gristick, H B]]
| + | [[Category: Homo sapiens]] |
| - | [[Category: Keeffe, J R]]
| + | [[Category: Large Structures]] |
| - | [[Category: West, A P]]
| + | [[Category: Bjorkman PJ]] |
| - | [[Category: Antibody]] | + | [[Category: Gristick HB]] |
| - | [[Category: Dengue]] | + | [[Category: Keeffe JR]] |
| - | [[Category: Fab]] | + | [[Category: West Jr AP]] |
| - | [[Category: Immune system]] | + | |
| - | [[Category: Neutralizing]] | + | |
| - | [[Category: Recurrent]] | + | |
| - | [[Category: Zika]]
| + | |
| Structural highlights
Function
S6B291_HUMAN
Publication Abstract from PubMed
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.
Recurrent Potent Human Neutralizing Antibodies to Zika Virus in Brazil and Mexico.,Robbiani DF, Bozzacco L, Keeffe JR, Khouri R, Olsen PC, Gazumyan A, Schaefer-Babajew D, Avila-Rios S, Nogueira L, Patel R, Azzopardi SA, Uhl LFK, Saeed M, Sevilla-Reyes EE, Agudelo M, Yao KH, Golijanin J, Gristick HB, Lee YE, Hurley A, Caskey M, Pai J, Oliveira T, Wunder EA Jr, Sacramento G, Nery N Jr, Orge C, Costa F, Reis MG, Thomas NM, Eisenreich T, Weinberger DM, de Almeida ARP, West AP Jr, Rice CM, Bjorkman PJ, Reyes-Teran G, Ko AI, MacDonald MR, Nussenzweig MC Cell. 2017 May 4;169(4):597-609.e11. doi: 10.1016/j.cell.2017.04.024. PMID:28475892[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Robbiani DF, Bozzacco L, Keeffe JR, Khouri R, Olsen PC, Gazumyan A, Schaefer-Babajew D, Avila-Rios S, Nogueira L, Patel R, Azzopardi SA, Uhl LFK, Saeed M, Sevilla-Reyes EE, Agudelo M, Yao KH, Golijanin J, Gristick HB, Lee YE, Hurley A, Caskey M, Pai J, Oliveira T, Wunder EA Jr, Sacramento G, Nery N Jr, Orge C, Costa F, Reis MG, Thomas NM, Eisenreich T, Weinberger DM, de Almeida ARP, West AP Jr, Rice CM, Bjorkman PJ, Reyes-Teran G, Ko AI, MacDonald MR, Nussenzweig MC. Recurrent Potent Human Neutralizing Antibodies to Zika Virus in Brazil and Mexico. Cell. 2017 May 4;169(4):597-609.e11. doi: 10.1016/j.cell.2017.04.024. PMID:28475892 doi:http://dx.doi.org/10.1016/j.cell.2017.04.024
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