[English] 日本語
Yorodumi- PDB-6mjz: Cryo-EM structure of Human Parainfluenza Virus Type 3 (hPIV3) in ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6mjz | ||||||
---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of Human Parainfluenza Virus Type 3 (hPIV3) in complex with antibody PIA174 | ||||||
Components |
| ||||||
Keywords | VIRAL PROTEIN/immune system / hPIV3 Envelope / asymmetric / complex / antibody / VIRAL PROTEIN / VIRAL PROTEIN-immune system complex | ||||||
Function / homology | Precursor fusion glycoprotein F0, Paramyxoviridae / Fusion glycoprotein F0 / fusion of virus membrane with host plasma membrane / viral envelope / host cell plasma membrane / virion membrane / plasma membrane / Fusion glycoprotein F0 Function and homology information | ||||||
Biological species | Human parainfluenza virus 3 Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.3 Å | ||||||
Authors | Acharya, P. / Stewart-Jones, G. / Carragher, B. / Potter, C.S. / Kwong, P.D. | ||||||
Citation | Journal: Proc Natl Acad Sci U S A / Year: 2018 Title: Structure-based design of a quadrivalent fusion glycoprotein vaccine for human parainfluenza virus types 1-4. Authors: Guillaume B E Stewart-Jones / Gwo-Yu Chuang / Kai Xu / Tongqing Zhou / Priyamvada Acharya / Yaroslav Tsybovsky / Li Ou / Baoshan Zhang / Blanca Fernandez-Rodriguez / Valentina Gilardi / ...Authors: Guillaume B E Stewart-Jones / Gwo-Yu Chuang / Kai Xu / Tongqing Zhou / Priyamvada Acharya / Yaroslav Tsybovsky / Li Ou / Baoshan Zhang / Blanca Fernandez-Rodriguez / Valentina Gilardi / Chiara Silacci-Fregni / Martina Beltramello / Ulrich Baxa / Aliaksandr Druz / Wing-Pui Kong / Paul V Thomas / Yongping Yang / Kathryn E Foulds / John-Paul Todd / Hui Wei / Andres M Salazar / Diana G Scorpio / Bridget Carragher / Clinton S Potter / Davide Corti / John R Mascola / Antonio Lanzavecchia / Peter D Kwong / Abstract: Parainfluenza virus types 1-4 (PIV1-4) are highly infectious human pathogens, of which PIV3 is most commonly responsible for severe respiratory illness in newborns, elderly, and immunocompromised ...Parainfluenza virus types 1-4 (PIV1-4) are highly infectious human pathogens, of which PIV3 is most commonly responsible for severe respiratory illness in newborns, elderly, and immunocompromised individuals. To obtain a vaccine effective against all four PIV types, we engineered mutations in each of the four PIV fusion (F) glycoproteins to stabilize their metastable prefusion states, as such stabilization had previously enabled the elicitation of high-titer neutralizing antibodies against the related respiratory syncytial virus. A cryoelectron microscopy structure of an engineered PIV3 F prefusion-stabilized trimer, bound to the prefusion-specific antibody PIA174, revealed atomic-level details for how introduced mutations improved stability as well as how a single PIA174 antibody recognized the trimeric apex of prefusion PIV3 F. Nine combinations of six newly identified disulfides and two cavity-filling mutations stabilized the prefusion PIV3 F immunogens and induced 200- to 500-fold higher neutralizing titers in mice than were elicited by PIV3 F in the postfusion conformation. For PIV1, PIV2, and PIV4, we also obtained stabilized prefusion Fs, for which prefusion versus postfusion titers were 2- to 20-fold higher. Elicited murine responses were PIV type-specific, with little cross-neutralization of other PIVs. In nonhuman primates (NHPs), quadrivalent immunization with prefusion-stabilized Fs from PIV1-4 consistently induced potent neutralizing responses against all four PIVs. For PIV3, the average elicited NHP titer from the quadrivalent immunization was more than fivefold higher than any titer observed in a cohort of over 100 human adults, highlighting the ability of a prefusion-stabilized immunogen to elicit especially potent neutralization. | ||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6mjz.cif.gz | 263.8 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb6mjz.ent.gz | 215.6 KB | Display | PDB format |
PDBx/mmJSON format | 6mjz.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6mjz_validation.pdf.gz | 675.9 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 6mjz_full_validation.pdf.gz | 690.1 KB | Display | |
Data in XML | 6mjz_validation.xml.gz | 44.8 KB | Display | |
Data in CIF | 6mjz_validation.cif.gz | 67.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/mj/6mjz ftp://data.pdbj.org/pub/pdb/validation_reports/mj/6mjz | HTTPS FTP |
-Related structure data
Related structure data | 9135MC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
#1: Protein | Mass: 54970.625 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human parainfluenza virus 3 / Gene: F, KMQ_34898gpF / Production host: Homo sapiens (human) / References: UniProt: A0A059QA82 #2: Antibody | | Mass: 23512.453 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #3: Antibody | | Mass: 22686.240 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Complex of hPIV3 Env Q162C-L168C, I213C-G230C, A463V, I474Y in complex with antibody PIA174 Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES |
---|---|
Molecular weight | Experimental value: NO |
Source (natural) | Organism: Human respirovirus 3 |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE / Humidity: 95 % |
-Electron microscopy imaging
Microscopy | Model: FEI TITAN |
---|---|
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 1.4 e/Å2 / Film or detector model: GATAN K2 QUANTUM (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.13_2998: / Classification: refinement | |||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EM software |
| |||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | |||||||||||||||||||||
3D reconstruction | Resolution: 4.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 97177 / Symmetry type: POINT | |||||||||||||||||||||
Refinement | Highest resolution: 4.3 Å |