+
Open data
-
Basic information
Entry | Database: PDB / ID: 6jhq | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | The cryo-EM structure of HAV bound to a neutralizing antibody-F4 | ||||||||||||
![]() |
| ||||||||||||
![]() | VIRUS / Icosahedral symmetry / neutralizing antibody / HAV / complex | ||||||||||||
Function / homology | ![]() host cell mitochondrial outer membrane / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / ribonucleoside triphosphate phosphatase activity / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / host multivesicular body / nucleoside-triphosphate phosphatase / protein complex oligomerization / monoatomic ion channel activity ...host cell mitochondrial outer membrane / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / ribonucleoside triphosphate phosphatase activity / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / host multivesicular body / nucleoside-triphosphate phosphatase / protein complex oligomerization / monoatomic ion channel activity / RNA helicase activity / symbiont entry into host cell / RNA-directed RNA polymerase / viral RNA genome replication / cysteine-type endopeptidase activity / RNA-dependent RNA polymerase activity / virus-mediated perturbation of host defense response / DNA-templated transcription / virion attachment to host cell / structural molecule activity / proteolysis / RNA binding / ATP binding / membrane Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å | ||||||||||||
![]() | Cao, L. / Liu, P. / Yang, P. / Gao, Q. / Li, H. / Sun, Y. / Zhu, L. / Lin, J. / Su, D. / Rao, Z. / Wang, X. | ||||||||||||
Funding support | ![]()
| ||||||||||||
![]() | ![]() Title: Structural basis for neutralization of hepatitis A virus informs a rational design of highly potent inhibitors. Authors: Lei Cao / Pi Liu / Pan Yang / Qiang Gao / Hong Li / Yao Sun / Ling Zhu / Jianping Lin / Dan Su / Zihe Rao / Xiangxi Wang / ![]() Abstract: Hepatitis A virus (HAV), an enigmatic and ancient pathogen, is a major causative agent of acute viral hepatitis worldwide. Although there are effective vaccines, antivirals against HAV infection are ...Hepatitis A virus (HAV), an enigmatic and ancient pathogen, is a major causative agent of acute viral hepatitis worldwide. Although there are effective vaccines, antivirals against HAV infection are still required, especially during fulminant hepatitis outbreaks. A more in-depth understanding of the antigenic characteristics of HAV and the mechanisms of neutralization could aid in the development of rationally designed antiviral drugs targeting HAV. In this paper, 4 new antibodies-F4, F6, F7, and F9-are reported that potently neutralize HAV at 50% neutralizing concentration values (neut50) ranging from 0.1 nM to 0.85 nM. High-resolution cryo-electron microscopy (cryo-EM) structures of HAV bound to F4, F6, F7, and F9, together with results of our previous studies on R10 fragment of antigen binding (Fab)-HAV complex, shed light on the locations and nature of the epitopes recognized by the 5 neutralizing monoclonal antibodies (NAbs). All the epitopes locate within the same patch and are highly conserved. The key structure-activity correlates based on the antigenic sites have been established. Based on the structural data of the single conserved antigenic site and key structure-activity correlates, one promising drug candidate named golvatinib was identified by in silico docking studies. Cell-based antiviral assays confirmed that golvatinib is capable of blocking HAV infection effectively with a 50% inhibitory concentration (IC50) of approximately 1 μM. These results suggest that the single conserved antigenic site from complete HAV capsid is a good antiviral target and that golvatinib could function as a lead compound for anti-HAV drug development. | ||||||||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | Molecule: ![]() ![]() |
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 206.1 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 169.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1012.8 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 1018.7 KB | Display | |
Data in XML | ![]() | 36.3 KB | Display | |
Data in CIF | ![]() | 55 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9827MC ![]() 9828C ![]() 9829C ![]() 9830C ![]() 6jhrC ![]() 6jhsC ![]() 6jhtC M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 | ![]()
| x 60
2 |
|
3 | ![]()
| x 5
4 | ![]()
| x 6
5 | ![]()
|
Symmetry | Point symmetry: (Schoenflies symbol: I (icosahedral)) |
-
Components
#1: Protein | Mass: 30820.629 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: P08617*PLUS |
---|---|
#2: Protein | Mass: 24898.172 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: P08617*PLUS |
#3: Protein | Mass: 27835.693 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: P08617*PLUS |
#4: Antibody | Mass: 23939.873 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#5: Antibody | Mass: 23592.875 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Source (natural) |
| ||||||||||||||||||||||||
Details of virus | Empty: NO / Enveloped: NO / Isolate: STRAIN / Type: VIRION | ||||||||||||||||||||||||
Buffer solution | pH: 7 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 1.3 e/Å2 / Film or detector model: GATAN K2 BASE (4k x 4k) |
-
Processing
Software | Name: PHENIX / Version: 1.11.1_2575: / Classification: refinement | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EM software | Name: PHENIX / Category: 3D reconstruction | ||||||||||||||||||||||||
CTF correction | Type: NONE | ||||||||||||||||||||||||
Symmetry | Point symmetry: I (icosahedral) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 4536 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
|