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Yorodumi- EMDB-9135: Cryo-EM structure of Human Parainfluenza Virus Type 3 (hPIV3) in ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-9135 | |||||||||
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Title | Cryo-EM structure of Human Parainfluenza Virus Type 3 (hPIV3) in complex with antibody PIA174 | |||||||||
Map data | ||||||||||
Sample |
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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 respirovirus 3 / Human parainfluenza virus 3 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.3 Å | |||||||||
Authors | Acharya P / Stewart-Jones G / Carragher B / Potter CS / Kwong PD | |||||||||
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 |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_9135.map.gz | 6.6 MB | EMDB map data format | |
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Header (meta data) | emd-9135-v30.xml emd-9135.xml | 14.4 KB 14.4 KB | Display Display | EMDB header |
Images | emd_9135.png | 104.4 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-9135 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9135 | HTTPS FTP |
-Validation report
Summary document | emd_9135_validation.pdf.gz | 303.5 KB | Display | EMDB validaton report |
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Full document | emd_9135_full_validation.pdf.gz | 303.1 KB | Display | |
Data in XML | emd_9135_validation.xml.gz | 6.5 KB | Display | |
Data in CIF | emd_9135_validation.cif.gz | 7.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9135 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9135 | HTTPS FTP |
-Related structure data
Related structure data | 6mjzMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_9135.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Complex of hPIV3 Env Q162C-L168C, I213C-G230C, A463V, I474Y in co...
Entire | Name: Complex of hPIV3 Env Q162C-L168C, I213C-G230C, A463V, I474Y in complex with antibody PIA174 |
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Components |
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-Supramolecule #1: Complex of hPIV3 Env Q162C-L168C, I213C-G230C, A463V, I474Y in co...
Supramolecule | Name: Complex of hPIV3 Env Q162C-L168C, I213C-G230C, A463V, I474Y in complex with antibody PIA174 type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Human respirovirus 3 |
-Macromolecule #1: Fusion glycoprotein F0
Macromolecule | Name: Fusion glycoprotein F0 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Human parainfluenza virus 3 |
Molecular weight | Theoretical: 54.970625 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QIDITKLQHV GVLVNSPKGM KISQNFETRY LILSLIPKIE DSNSCGDQQI KQYKRLLDRL IIPLYDGLKL QKDVIVTNQE SNENTDPRT ERFFGGVIGT IALGVATSAQ ITAAVALVEA KQAKSDIEKL KEAIRDTNKA VQSVCSSVGN CIVAIKSVQD Y VNKEIVPS ...String: QIDITKLQHV GVLVNSPKGM KISQNFETRY LILSLIPKIE DSNSCGDQQI KQYKRLLDRL IIPLYDGLKL QKDVIVTNQE SNENTDPRT ERFFGGVIGT IALGVATSAQ ITAAVALVEA KQAKSDIEKL KEAIRDTNKA VQSVCSSVGN CIVAIKSVQD Y VNKEIVPS IARLGCEAAG LQLGIALTQH YSELTNCFGD NIGSLQEKGI KLQCIASLYR TNITEIFTTS TVDKYDIYDL LF TESIKVR VIDVDLNDYS ITLQVRLPLL TRLLNTQIYK VDSISYNIQN REWYIPLPSH IMTKGAFLGG ADVKECIEAF SSY ICPSDP GFVLNHEMES CLSGNISQCP RTTVTSDIVP RYAFVNGGVV ANCITTTCTC NGIGNRINQP PDQGVKIITH KECN TIGIN GMLFNTNKEG TLAFYTPDDI TLNNSVALDP IDISIELNKV KSDLEESKEW YRRSNQKLSA IEDKIEEILS KIYHI ENEI ARIKKLIGEA P |
-Macromolecule #2: PIA174 Fab Heavy chain
Macromolecule | Name: PIA174 Fab Heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.512453 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: VQLQESGPGL VKPSETLSLT CTVSGGSVSS YYWSWIRQPP GKGLEWIGNI YYSGTTKYNP SLKSRVTISV DVSKNQFSLN LISVTAADT AVYFCARQVK SGWFVQPFDY WGQGALVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV S WNSGALTS ...String: VQLQESGPGL VKPSETLSLT CTVSGGSVSS YYWSWIRQPP GKGLEWIGNI YYSGTTKYNP SLKSRVTISV DVSKNQFSLN LISVTAADT AVYFCARQVK SGWFVQPFDY WGQGALVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV S WNSGALTS GVHTFPAVLQ SSGLYSLSSV VTVPSSSLGT QTYICNVNHK PSNTKVDKKV EPK |
-Macromolecule #3: PIA174 Fab Light chain
Macromolecule | Name: PIA174 Fab Light chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 22.68624 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QMTQSPPSLS AYVGDRVTIT CRASQAIANY LAWFQQKPGK APKSLIYAAS TLQSGVPSRF SGSGSGTDFT LTISSLQPED FATYYCHQY NTYPITFGQG TRLEIKRRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ E SVTEQDSK ...String: QMTQSPPSLS AYVGDRVTIT CRASQAIANY LAWFQQKPGK APKSLIYAAS TLQSGVPSRF SGSGSGTDFT LTISSLQPED FATYYCHQY NTYPITFGQG TRLEIKRRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ E SVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ GLSSPVTKS |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 1 mg/mL |
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Buffer | pH: 7.5 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 95 % |
-Electron microscopy
Microscope | FEI TITAN |
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Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Average electron dose: 1.4 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |