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Yorodumi- EMDB-29908: Structure of human NDS.1 Fab and 1G01 Fab in complex with influen... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-29908 | |||||||||
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Title | Structure of human NDS.1 Fab and 1G01 Fab in complex with influenza virus neuraminidase from A/Indiana/10/2011 (H3N2v), locally refined map | |||||||||
Map data | Map post-processed with DeepEMhancer | |||||||||
Sample |
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Keywords | neuraminidase / antibody / influenza / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | Function and homology information profilin binding / Signaling by ROBO receptors / Cell-extracellular matrix interactions / actin polymerization or depolymerization / filopodium membrane / positive regulation of actin filament polymerization / exo-alpha-(2->3)-sialidase activity / exo-alpha-(2->6)-sialidase activity / exo-alpha-(2->8)-sialidase activity / exo-alpha-sialidase ...profilin binding / Signaling by ROBO receptors / Cell-extracellular matrix interactions / actin polymerization or depolymerization / filopodium membrane / positive regulation of actin filament polymerization / exo-alpha-(2->3)-sialidase activity / exo-alpha-(2->6)-sialidase activity / exo-alpha-(2->8)-sialidase activity / exo-alpha-sialidase / lamellipodium membrane / Generation of second messenger molecules / bicellular tight junction / viral budding from plasma membrane / neural tube closure / axon guidance / SH3 domain binding / actin cytoskeleton / actin binding / actin cytoskeleton organization / protein homotetramerization / carbohydrate metabolic process / cadherin binding / focal adhesion / host cell plasma membrane / virion membrane / extracellular exosome / membrane / metal ion binding / plasma membrane / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Influenza A virus (A/Indiana/10/2011(H3N2)) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.6 Å | |||||||||
Authors | Tsybovsky Y / Lederhofer J / Kwong PD / Kanekiyo M | |||||||||
Funding support | 1 items
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Citation | Journal: Immunity / Year: 2024 Title: Protective human monoclonal antibodies target conserved sites of vulnerability on the underside of influenza virus neuraminidase. Authors: Julia Lederhofer / Yaroslav Tsybovsky / Lam Nguyen / Julie E Raab / Adrian Creanga / Tyler Stephens / Rebecca A Gillespie / Hubza Z Syeda / Brian E Fisher / Michelle Skertic / Christina Yap ...Authors: Julia Lederhofer / Yaroslav Tsybovsky / Lam Nguyen / Julie E Raab / Adrian Creanga / Tyler Stephens / Rebecca A Gillespie / Hubza Z Syeda / Brian E Fisher / Michelle Skertic / Christina Yap / Andrew J Schaub / Reda Rawi / Peter D Kwong / Barney S Graham / Adrian B McDermott / Sarah F Andrews / Neil P King / Masaru Kanekiyo / Abstract: Continuously evolving influenza viruses cause seasonal epidemics and pose global pandemic threats. Although viral neuraminidase (NA) is an effective drug and vaccine target, our understanding of the ...Continuously evolving influenza viruses cause seasonal epidemics and pose global pandemic threats. Although viral neuraminidase (NA) is an effective drug and vaccine target, our understanding of the NA antigenic landscape still remains incomplete. Here, we describe NA-specific human antibodies that target the underside of the NA globular head domain, inhibit viral propagation of a wide range of human H3N2, swine-origin variant H3N2, and H2N2 viruses, and confer both pre- and post-exposure protection against lethal H3N2 infection in mice. Cryo-EM structures of two such antibodies in complex with NA reveal non-overlapping epitopes covering the underside of the NA head. These sites are highly conserved among N2 NAs yet inaccessible unless the NA head tilts or dissociates. Our findings help guide the development of effective countermeasures against ever-changing influenza viruses by identifying hidden conserved sites of vulnerability on the NA underside. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_29908.map.gz | 33.6 MB | EMDB map data format | |
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Header (meta data) | emd-29908-v30.xml emd-29908.xml | 25.7 KB 25.7 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_29908_fsc.xml | 7.7 KB | Display | FSC data file |
Images | emd_29908.png | 39.6 KB | ||
Masks | emd_29908_msk_1.map | 38.4 MB | Mask map | |
Filedesc metadata | emd-29908.cif.gz | 7 KB | ||
Others | emd_29908_additional_1.map.gz emd_29908_additional_2.map.gz emd_29908_half_map_1.map.gz emd_29908_half_map_2.map.gz | 29.6 MB 3.2 MB 29.6 MB 29.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-29908 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-29908 | HTTPS FTP |
-Related structure data
Related structure data | 8gauMC 8gatC 8gavC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_29908.map.gz / Format: CCP4 / Size: 38.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Map post-processed with DeepEMhancer | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.11 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_29908_msk_1.map | ||||||||||||
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Density Histograms |
-Additional map: Map before post-processing
File | emd_29908_additional_1.map | ||||||||||||
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Annotation | Map before post-processing | ||||||||||||
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Density Histograms |
-Additional map: Map automatically post-processed with Relion
File | emd_29908_additional_2.map | ||||||||||||
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Annotation | Map automatically post-processed with Relion | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half-map 1
File | emd_29908_half_map_1.map | ||||||||||||
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Annotation | Half-map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half-map 2
File | emd_29908_half_map_2.map | ||||||||||||
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Annotation | Half-map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Influenza virus neuraminidase from A/Indiana/10/2011 (H3N2v) in c...
Entire | Name: Influenza virus neuraminidase from A/Indiana/10/2011 (H3N2v) in complex with Fabs NDS.1 and 1G01 |
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Components |
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-Supramolecule #1: Influenza virus neuraminidase from A/Indiana/10/2011 (H3N2v) in c...
Supramolecule | Name: Influenza virus neuraminidase from A/Indiana/10/2011 (H3N2v) in complex with Fabs NDS.1 and 1G01 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 580 KDa |
-Macromolecule #1: Vasodilator-stimulated phosphoprotein, Neuraminidase chimera
Macromolecule | Name: Vasodilator-stimulated phosphoprotein, Neuraminidase chimera type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: exo-alpha-sialidase |
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Source (natural) | Organism: Influenza A virus (A/Indiana/10/2011(H3N2)) / Strain: A/Indiana/10/2011(H3N2) |
Molecular weight | Theoretical: 51.799113 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MEFGLSWIFL AAILKGVQCA DPHHHHHHSS SDYSDLQRVK QELLEEVKKE LQKVKEEIIE AFVQELRKRG SLVPRGSGGE YRNWSKPQC NITGFAPFSK DNSIRLSAGG DIWVTREPYV SCDPDKCYQF ALGQGTTLNN GHSNNTVHDR TPYRTLLMNE L GVPFHLGT ...String: MEFGLSWIFL AAILKGVQCA DPHHHHHHSS SDYSDLQRVK QELLEEVKKE LQKVKEEIIE AFVQELRKRG SLVPRGSGGE YRNWSKPQC NITGFAPFSK DNSIRLSAGG DIWVTREPYV SCDPDKCYQF ALGQGTTLNN GHSNNTVHDR TPYRTLLMNE L GVPFHLGT RQVCMAWSSS SCHDGKAWLH VCITGNDNNA TASFIYNGRL VDSIGSWSKN ILRTQESECV CINGTCTVVM TD GSASGKA DTKILFVEEG KIVHISTLSG SAQHVEECSC YPRFPGVRCV CRDNWKGSNR PIVDINVKNY SIVSSYVCSG LVG DTPRKS DSVSSSYCLD PNNEKGGHGV KGWAFDDGND VWMGRTINET LRLGYETFKV IEGWSKANSK LQTNRQVIVE KGDR SGYSG IFSVEGKSCI NRCFYVELIR GRKEETKVWW TSNSIVVFCG TSGTYGTGSW PDGADINLMP I UniProtKB: Vasodilator-stimulated phosphoprotein, Neuraminidase |
-Macromolecule #2: Fab NDS.1, heavy chain
Macromolecule | Name: Fab NDS.1, 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: 24.597711 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLRQWGAG LLKPSETLSL TCDVYGGSFN FYFWTWIRQP PGKGLEWLGE ITHSGSATYI PSLKSRVTLS VDTSKGQFSL KLTSVNVAD TAVYYCAGLP IDYDTVHLGY YPMDVWGQGT PVTVSSASTK GPSVFPLAPS SKSTSGGTAA LGCLVKDYFP E PVTVSWNS ...String: QVQLRQWGAG LLKPSETLSL TCDVYGGSFN FYFWTWIRQP PGKGLEWLGE ITHSGSATYI PSLKSRVTLS VDTSKGQFSL KLTSVNVAD TAVYYCAGLP IDYDTVHLGY YPMDVWGQGT PVTVSSASTK GPSVFPLAPS SKSTSGGTAA LGCLVKDYFP E PVTVSWNS GALTSGVHTF PAVLQSSGLY SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VDKKVEPKSC DK |
-Macromolecule #3: Fab NDS.1, light chain
Macromolecule | Name: Fab NDS.1, 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: 23.356955 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DIQMTQSPSS LSASVGDRVT ITCRASQGIR NYLAWYQQKP GKVPKLLIYG ASTLQSGVPS RFSGSGSGTD FSLTISSLQP EDIATYFCQ EYNNAPRTFG QGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String: DIQMTQSPSS LSASVGDRVT ITCRASQGIR NYLAWYQQKP GKVPKLLIYG ASTLQSGVPS RFSGSGSGTD FSLTISSLQP EDIATYFCQ EYNNAPRTFG QGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC |
-Macromolecule #4: Fab 1G01, heavy chain
Macromolecule | Name: Fab 1G01, heavy chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 25.981021 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DEVQLVESGG RALRPGGSLR LSCAASGFKF DDYAMSWVRQ VPGKGLEFVS GLNWNGDITA YTDSVKGRFT VSRDNAKNSL YLHINSPKP EDTALYYCAR TSSWGDYTRG PEPKITWYFD LWGRGTLVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL V KDYFPEPV ...String: DEVQLVESGG RALRPGGSLR LSCAASGFKF DDYAMSWVRQ VPGKGLEFVS GLNWNGDITA YTDSVKGRFT VSRDNAKNSL YLHINSPKP EDTALYYCAR TSSWGDYTRG PEPKITWYFD LWGRGTLVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL V KDYFPEPV TVSWNSGALT SGVHTFPAVL QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKR VEPKSCHHHH HH |
-Macromolecule #5: Fab 1G01, light chain
Macromolecule | Name: Fab 1G01, light chain / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.677273 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DDIQLTQSPS FLSASVGDRI TITCRASQGI DGYLAWYQQR PGKAPNLLIY AASLLQSGVP SRFSGSGYGT EFTLTISSLQ PEDFATYYC QHLDSYPLFT FGPGTKVDIK RTVAAPSVFI FPPSDEQLKS GTASVVCLLN NFYPREAKVQ WKVDNALQSG N SQESVTEQ ...String: DDIQLTQSPS FLSASVGDRI TITCRASQGI DGYLAWYQQR PGKAPNLLIY AASLLQSGVP SRFSGSGYGT EFTLTISSLQ PEDFATYYC QHLDSYPLFT FGPGTKVDIK RTVAAPSVFI FPPSDEQLKS GTASVVCLLN NFYPREAKVQ WKVDNALQSG N SQESVTEQ DSKDSTYSLS STLTLSKADY EKHKVYACEV THQGLSSPVT KSFNRGEC |
-Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 1 / 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
Concentration | 0.15 mg/mL |
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Buffer | pH: 7 |
Vitrification | Cryogen name: NITROGEN |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 40.0 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: 3.0 µm / Nominal defocus min: 1.0 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Initial model | Chain - Source name: SwissModel / Chain - Initial model type: in silico model |
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Refinement | Space: REAL / Protocol: BACKBONE TRACE |
Output model | PDB-8gau: |