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- PDB-7cth: Cryo-EM structure of dengue virus serotype 2 in complex with the ... -
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Basic information
Entry | Database: PDB / ID: 7cth | ||||||||||||
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Title | Cryo-EM structure of dengue virus serotype 2 in complex with the scFv fragment of the broadly neutralizing antibody EDE1 C10 | ||||||||||||
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![]() | VIRUS / Dengue virus / antibody / broadly neutralizing / flavivirus | ||||||||||||
Function / homology | ![]() : / flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / membrane => GO:0016020 / RNA helicase activity ...: / flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / membrane => GO:0016020 / RNA helicase activity / host cell endoplasmic reticulum membrane / protein dimerization activity / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / RNA helicase / induction by virus of host autophagy / serine-type endopeptidase activity / viral RNA genome replication / RNA-dependent RNA polymerase activity / fusion of virus membrane with host endosome membrane / host cell nucleus / virion attachment to host cell / structural molecule activity / virion membrane / extracellular region / ATP binding / metal ion binding Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||||||||
![]() | Zhang, X. / Sharma, A. / Duquerroy, S. / Zhou, Z.H. / Rey, F.A. | ||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: The epitope arrangement on flavivirus particles contributes to Mab C10's extraordinary neutralization breadth across Zika and dengue viruses. Authors: Arvind Sharma / Xiaokang Zhang / Wanwisa Dejnirattisai / Xinghong Dai / Danyang Gong / Wiyada Wongwiwat / Stéphane Duquerroy / Alexander Rouvinski / Marie-Christine Vaney / Pablo Guardado- ...Authors: Arvind Sharma / Xiaokang Zhang / Wanwisa Dejnirattisai / Xinghong Dai / Danyang Gong / Wiyada Wongwiwat / Stéphane Duquerroy / Alexander Rouvinski / Marie-Christine Vaney / Pablo Guardado-Calvo / Ahmed Haouz / Patrick England / Ren Sun / Z Hong Zhou / Juthathip Mongkolsapaya / Gavin R Screaton / Felix A Rey / ![]() ![]() ![]() ![]() ![]() Abstract: The human monoclonal antibody C10 exhibits extraordinary cross-reactivity, potently neutralizing Zika virus (ZIKV) and the four serotypes of dengue virus (DENV1-DENV4). Here we describe a comparative ...The human monoclonal antibody C10 exhibits extraordinary cross-reactivity, potently neutralizing Zika virus (ZIKV) and the four serotypes of dengue virus (DENV1-DENV4). Here we describe a comparative structure-function analysis of C10 bound to the envelope (E) protein dimers of the five viruses it neutralizes. We demonstrate that the C10 Fab has high affinity for ZIKV and DENV1 but not for DENV2, DENV3, and DENV4. We further show that the C10 interaction with the latter viruses requires an E protein conformational landscape that limits binding to only one of the three independent epitopes per virion. This limited affinity is nevertheless counterbalanced by the particle's icosahedral organization, which allows two different dimers to be reached by both Fab arms of a C10 immunoglobulin. The epitopes' geometric distribution thus confers C10 its exceptional neutralization breadth. Our results highlight the importance not only of paratope/epitope complementarity but also the topological distribution for epitope-focused vaccine design. #1: ![]() Title: Structural basis of potent Zika-dengue virus antibody cross-neutralization. Authors: Barba-Spaeth, G. / Dejnirattisai, W. / Rouvinski, A. / Vaney, M.C. / Medits, I. / Sharma, A. / Simon-Loriere, E. / Sakuntabhai, A. / Cao-Lormeau, V.M. / Haouz, A. / England, P. / Stiasny, K. ...Authors: Barba-Spaeth, G. / Dejnirattisai, W. / Rouvinski, A. / Vaney, M.C. / Medits, I. / Sharma, A. / Simon-Loriere, E. / Sakuntabhai, A. / Cao-Lormeau, V.M. / Haouz, A. / England, P. / Stiasny, K. / Mongkolsapaya, J. / Heinz, F.X. / Screaton, G.R. / Rey, F.A. | ||||||||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 399.3 KB | Display | ![]() |
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PDB format | ![]() | 335.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 1.4 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 85.4 KB | Display | |
Data in CIF | ![]() | 124.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 30465MC ![]() 7a3nC ![]() 7a3oC ![]() 7a3pC ![]() 7a3qC ![]() 7a3rC ![]() 7a3sC ![]() 7a3tC ![]() 7a3uC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
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Symmetry | Point symmetry: (Schoenflies symbol: I (icosahedral)) |
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Components
#1: Protein | Mass: 54351.746 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Protein | Mass: 8345.762 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: Q20II5, flavivirin, nucleoside-triphosphate phosphatase, RNA helicase #3: Antibody | Mass: 15679.234 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Details: heavy chain variable region of the broadly neutralizing antibody EDE1 C10 Source: (gene. exp.) ![]() ![]() ![]() #4: Antibody | Mass: 15632.767 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Details: light chain variable region of the broadly neutralizing antibody EDE1 C10 Source: (gene. exp.) ![]() ![]() ![]() #5: Sugar | ChemComp-NAG / Has ligand of interest | N | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Dengue virus / Type: VIRUS / Entity ID: #2-#4 / Source: NATURAL |
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Source (natural) | Organism: ![]() ![]() |
Details of virus | Empty: NO / Enveloped: YES / Isolate: SEROTYPE / Type: VIRION |
Natural host | Organism: Homo sapiens |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Cs: 2.7 mm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 60 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: I (icosahedral) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 4977 / Algorithm: FOURIER SPACE / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||
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