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Yorodumi- EMDB-26458: Structure of lineage I (Pinneo) Lassa virus glycoprotein bound to... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-26458 | ||||||||||||
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Title | Structure of lineage I (Pinneo) Lassa virus glycoprotein bound to Fab 25.10C | ||||||||||||
Map data | Sharpened map | ||||||||||||
Sample |
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Function / homology | Function and homology information host cell Golgi membrane / membrane => GO:0016020 / receptor-mediated endocytosis of virus by host cell / host cell endoplasmic reticulum membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane / metal ion binding Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) / Lassa mammarenavirus | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | ||||||||||||
Authors | Buck TK / Enriquez AE / Hastie KM | ||||||||||||
Funding support | United States, 3 items
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Citation | Journal: mBio / Year: 2022 Title: Neutralizing Antibodies against Lassa Virus Lineage I. Authors: Tierra K Buck / Adrian S Enriquez / Sharon L Schendel / Michelle A Zandonatti / Stephanie S Harkins / Haoyang Li / Alex Moon-Walker / James E Robinson / Luis M Branco / Robert F Garry / ...Authors: Tierra K Buck / Adrian S Enriquez / Sharon L Schendel / Michelle A Zandonatti / Stephanie S Harkins / Haoyang Li / Alex Moon-Walker / James E Robinson / Luis M Branco / Robert F Garry / Erica Ollmann Saphire / Kathryn M Hastie / Abstract: Lassa virus (LASV) is the causative agent of the deadly Lassa fever (LF). Seven distinct LASV lineages circulate through western Africa, among which lineage I (LI), the first to be identified, is ...Lassa virus (LASV) is the causative agent of the deadly Lassa fever (LF). Seven distinct LASV lineages circulate through western Africa, among which lineage I (LI), the first to be identified, is particularly resistant to antibody neutralization. Lineage I LASV evades neutralization by half of known antibodies in the GPC-A antibody competition group and all but one of the antibodies in the GPC-B competition group. Here, we solve two cryo-electron microscopy (cryo-EM) structures of LI GP in complex with a GPC-A and a GPC-B antibody. We used complementary structural and biochemical techniques to identify single-amino-acid substitutions in LI that are responsible for immune evasion by each antibody group. Further, we show that LI infection is more dependent on the endosomal receptor lysosome-associated membrane protein 1 (LAMP1) for viral entry relative to LIV. In the absence of LAMP1, LI requires a more acidic fusion pH to initiate membrane fusion with the host cell relative to LIV. No vaccine or therapeutics are approved to prevent LASV infection or treat LF. All vaccine platforms currently under development present only the LIV GP sequence. However, our data suggest that the high genetic diversity of LASV may be problematic for designing both a broadly reactive immunogen and therapeutic. Here, we examine antibodies that are highly potent against LIV yet are ineffective against LI. By pinpointing LI mutations responsible for this decrease in antibody efficacy, we suggest that future vaccine platforms may need to incorporate specific LI-like mutations in order to generate a broadly neutralizing antibody response against all LASV lineages. | ||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_26458.map.gz | 191.9 MB | EMDB map data format | |
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Header (meta data) | emd-26458-v30.xml emd-26458.xml | 21.2 KB 21.2 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_26458_fsc.xml | 13.3 KB | Display | FSC data file |
Images | emd_26458.png | 43 KB | ||
Others | emd_26458_additional_1.map.gz emd_26458_half_map_1.map.gz emd_26458_half_map_2.map.gz | 108.3 MB 200.1 MB 200.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-26458 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26458 | HTTPS FTP |
-Validation report
Summary document | emd_26458_validation.pdf.gz | 801.1 KB | Display | EMDB validaton report |
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Full document | emd_26458_full_validation.pdf.gz | 800.7 KB | Display | |
Data in XML | emd_26458_validation.xml.gz | 21.3 KB | Display | |
Data in CIF | emd_26458_validation.cif.gz | 27.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26458 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26458 | HTTPS FTP |
-Related structure data
Related structure data | 7udsMC 7ul7C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_26458.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | Sharpened map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.096 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: Unsharpened map
File | emd_26458_additional_1.map | ||||||||||||
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Annotation | Unsharpened map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map A
File | emd_26458_half_map_1.map | ||||||||||||
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Annotation | Half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map B
File | emd_26458_half_map_2.map | ||||||||||||
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Annotation | Half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Lineage I Lassa virus glycoprotein bound to Fab 25.10C
Entire | Name: Lineage I Lassa virus glycoprotein bound to Fab 25.10C |
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Components |
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-Supramolecule #1: Lineage I Lassa virus glycoprotein bound to Fab 25.10C
Supramolecule | Name: Lineage I Lassa virus glycoprotein bound to Fab 25.10C type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Molecular weight | Experimental: 350 KDa |
-Macromolecule #1: 25.10C Fab Heavy Chain
Macromolecule | Name: 25.10C Fab Heavy Chain / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 24.27025 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: QVQLQESGGG LVKPGGSLRL SCTASGFNFN KYNMNWVRQA PGKGLEWVSS ISALSTYIYY ADSLKGRFTV SRDNAKNSLF LQMNSLRDD DTAVYYCARE IRRASTWSAD LWGRGTLVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPEPVT V SWNSGALT ...String: QVQLQESGGG LVKPGGSLRL SCTASGFNFN KYNMNWVRQA PGKGLEWVSS ISALSTYIYY ADSLKGRFTV SRDNAKNSLF LQMNSLRDD DTAVYYCARE IRRASTWSAD LWGRGTLVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPEPVT V SWNSGALT SGVHTFPAVL QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKR VEPKSCDK |
-Macromolecule #2: 25.10C Fab Light Chain
Macromolecule | Name: 25.10C Fab Light Chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 22.812377 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: IQMTQSPSSL SASVGDRVII TCRASQSISS SLNWYQQKPG KAPKLLIYAA VNLETGVPSR FSGSGFGTDF TLAISNVQPE DFATYYCQQ SDTRTFGRGT KLDVKRTVAA PSVFIFPPSD EQLKSGTASV VCLLNNFYPR EAKVQWKVDN ALQSGNSQES V TEQDSKDS ...String: IQMTQSPSSL SASVGDRVII TCRASQSISS SLNWYQQKPG KAPKLLIYAA VNLETGVPSR FSGSGFGTDF TLAISNVQPE DFATYYCQQ SDTRTFGRGT KLDVKRTVAA PSVFIFPPSD EQLKSGTASV VCLLNNFYPR EAKVQWKVDN ALQSGNSQES V TEQDSKDS TYSLSSTLTL SKADYEKHKV YACEVTHQGL SSPVTKSFNR G |
-Macromolecule #3: Glycoprotein G1
Macromolecule | Name: Glycoprotein G1 / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Lassa mammarenavirus |
Molecular weight | Theoretical: 28.987398 KDa |
Recombinant expression | Organism: Drosophila melanogaster (fruit fly) |
Sequence | String: MGQIITFFQE VPHVIEEVMN IVLIALSLLA ILKGLYNIAT CGIIGLVAFL FLCGKSCSLT LKGGYELQTL ELNMETLNMT MPLSCTKNS SHHYIRVGNE TGLELTLTNT SIINHKFCNL SDAHKKNLYD HALMSIISTF HLSIPNFNQY EAMSCDFNGG K ISVQYNLS ...String: MGQIITFFQE VPHVIEEVMN IVLIALSLLA ILKGLYNIAT CGIIGLVAFL FLCGKSCSLT LKGGYELQTL ELNMETLNMT MPLSCTKNS SHHYIRVGNE TGLELTLTNT SIINHKFCNL SDAHKKNLYD HALMSIISTF HLSIPNFNQY EAMSCDFNGG K ISVQYNLS HSYAGDAAEH CGTVANGVLQ TFMRMAWGGR YIALDSGCGN WDCIMTSYQY LIIQNTTWED HCQFSRPSPI GY LGLLSQR TRDIYISRRR R |
-Macromolecule #4: Glycoprotein G2
Macromolecule | Name: Glycoprotein G2 / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Lassa mammarenavirus |
Molecular weight | Theoretical: 23.348145 KDa |
Recombinant expression | Organism: Drosophila melanogaster (fruit fly) |
Sequence | String: GTFTWTLSDS EGNETPGGYC LTRWMLIEAE LKCFGNTAVA KCNEKHDEEF CDMLRLFDFN KQAIRRLKAP AQMSIQLINK AVNALINDQ LIMKNHLRDI MCIPYCNYSK YWYLNHTSSG RTSLPKCWLI SNGSYLNETQ FSDDIEQQAD NMITEMLQKE Y LPETGLVD ...String: GTFTWTLSDS EGNETPGGYC LTRWMLIEAE LKCFGNTAVA KCNEKHDEEF CDMLRLFDFN KQAIRRLKAP AQMSIQLINK AVNALINDQ LIMKNHLRDI MCIPYCNYSK YWYLNHTSSG RTSLPKCWLI SNGSYLNETQ FSDDIEQQAD NMITEMLQKE Y LPETGLVD LEVDDDDKAG WSHPQFEKGG GSGGGSGGGS WSHPQFEK |
-Macromolecule #8: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 8 / Number of copies: 10 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 Component:
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 298 K |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 55.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |