[English] 日本語
![](img/lk-miru.gif)
- PDB-8dv6: Zika virus envelope protein structure in complex with a potent Hu... -
+
Open data
-
Basic information
Entry | Database: PDB / ID: 8dv6 | ||||||
---|---|---|---|---|---|---|---|
Title | Zika virus envelope protein structure in complex with a potent Human mAb | ||||||
![]() |
| ||||||
![]() | VIRAL PROTEIN / Zika virus / envelope protein / neutralizing antibody / neutralization mechanism / flavivirus / VIRAL PROTEIN-Immune System complex | ||||||
Function / homology | ![]() symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / ribonucleoside triphosphate phosphatase activity / double-stranded RNA binding / viral capsid / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / RNA helicase activity / host cell endoplasmic reticulum membrane / protein dimerization activity / symbiont-mediated suppression of host type I interferon-mediated signaling pathway ...symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / ribonucleoside triphosphate phosphatase activity / double-stranded RNA binding / viral capsid / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / RNA helicase activity / host cell endoplasmic reticulum membrane / protein dimerization activity / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / symbiont entry into host cell / viral RNA genome replication / serine-type endopeptidase activity / RNA-dependent RNA polymerase activity / fusion of virus membrane with host endosome membrane / virion attachment to host cell / virion membrane / structural molecule activity / proteolysis / extracellular region / ATP binding / membrane / metal ion binding Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Cameron, A. / Puhl, A.C. / deSilva, A.M. / Premkumar, L. | ||||||
Funding support | ![]()
| ||||||
![]() | ![]() Title: Structure and neutralization mechanism of a human antibody targeting a complex Epitope on Zika virus. Authors: Cameron Adams / Derek L Carbaugh / Bo Shu / Thiam-Seng Ng / Izabella N Castillo / Ryan Bhowmik / Bruno Segovia-Chumbez / Ana C Puhl / Stephen Graham / Sean A Diehl / Helen M Lazear / Shee- ...Authors: Cameron Adams / Derek L Carbaugh / Bo Shu / Thiam-Seng Ng / Izabella N Castillo / Ryan Bhowmik / Bruno Segovia-Chumbez / Ana C Puhl / Stephen Graham / Sean A Diehl / Helen M Lazear / Shee-Mei Lok / Aravinda M de Silva / Lakshmanane Premkumar / ![]() ![]() Abstract: We currently have an incomplete understanding of why only a fraction of human antibodies that bind to flaviviruses block infection of cells. Here we define the footprint of a strongly neutralizing ...We currently have an incomplete understanding of why only a fraction of human antibodies that bind to flaviviruses block infection of cells. Here we define the footprint of a strongly neutralizing human monoclonal antibody (mAb G9E) with Zika virus (ZIKV) by both X-ray crystallography and cryo-electron microscopy. Flavivirus envelope (E) glycoproteins are present as homodimers on the virion surface, and G9E bound to a quaternary structure epitope spanning both E protomers forming a homodimer. As G9E mainly neutralized ZIKV by blocking a step after viral attachment to cells, we tested if the neutralization mechanism of G9E was dependent on the mAb cross-linking E molecules and blocking low-pH triggered conformational changes required for viral membrane fusion. We introduced targeted mutations to the G9E paratope to create recombinant antibodies that bound to the ZIKV envelope without cross-linking E protomers. The G9E paratope mutants that bound to a restricted epitope on one protomer poorly neutralized ZIKV compared to the wild-type mAb, demonstrating that the neutralization mechanism depended on the ability of G9E to cross-link E proteins. In cell-free low pH triggered viral fusion assay, both wild-type G9E, and epitope restricted paratope mutant G9E bound to ZIKV but only the wild-type G9E blocked fusion. We propose that, beyond antibody binding strength, the ability of human antibodies to cross-link E-proteins is a critical determinant of flavivirus neutralization potency. | ||||||
History |
|
-
Structure visualization
Structure viewer | Molecule: ![]() ![]() |
---|
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 780.7 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 461.9 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 474.5 KB | Display | |
Data in XML | ![]() | 56.5 KB | Display | |
Data in CIF | ![]() | 75.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7yarC ![]() 5jhmS S: Starting model for refinement C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
-
Assembly
Deposited unit | ![]()
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Unit cell |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments:
|