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Yorodumi- EMDB-42482: I53_dn5 nanoparticle displaying the trimeric HA heads with heptad... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-42482 | |||||||||
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Title | I53_dn5 nanoparticle displaying the trimeric HA heads with heptad domain, TH-1heptad-I53_dn5 (local refinement of TH-1heptad) | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Influenza virus / Hemagglutinin nanoparticle vaccine / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / VIRAL PROTEIN | |||||||||
Function / homology | Function and homology information viral budding from plasma membrane / clathrin-dependent endocytosis of virus by host cell / host cell surface receptor binding / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane / membrane Similarity search - Function | |||||||||
Biological species | synthetic construct (others) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.7 Å | |||||||||
Authors | Park YJ / Veesler D | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Cell Rep / Year: 2023 Title: Antigen spacing on protein nanoparticles influences antibody responses to vaccination. Authors: Daniel Ellis / Annie Dosey / Seyhan Boyoglu-Barnum / Young-Jun Park / Rebecca Gillespie / Hubza Syeda / Geoffrey B Hutchinson / Yaroslav Tsybovsky / Michael Murphy / Deleah Pettie / Nick ...Authors: Daniel Ellis / Annie Dosey / Seyhan Boyoglu-Barnum / Young-Jun Park / Rebecca Gillespie / Hubza Syeda / Geoffrey B Hutchinson / Yaroslav Tsybovsky / Michael Murphy / Deleah Pettie / Nick Matheson / Sidney Chan / George Ueda / Jorge A Fallas / Lauren Carter / Barney S Graham / David Veesler / Masaru Kanekiyo / Neil P King / Abstract: Immunogen design approaches aim to control the specificity and quality of antibody responses elicited by next-generation vaccines. Here, we use computational protein design to generate a nanoparticle ...Immunogen design approaches aim to control the specificity and quality of antibody responses elicited by next-generation vaccines. Here, we use computational protein design to generate a nanoparticle vaccine platform based on the receptor-binding domain (RBD) of influenza hemagglutinin (HA) that enables precise control of antigen conformation and spacing. HA RBDs are presented as either monomers or native-like closed trimers that are connected to the underlying nanoparticle by a rigid linker that is modularly extended to precisely control antigen spacing. Nanoparticle immunogens with decreased spacing between trimeric RBDs elicit antibodies with improved hemagglutination inhibition and neutralization potency as well as binding breadth across diverse H1 HAs. Our "trihead" nanoparticle immunogen platform provides insights into anti-HA immunity, establishes antigen spacing as an important parameter in structure-based vaccine design, and embodies several design features that could be used in next-generation vaccines against influenza and other viruses. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_42482.map.gz | 20.8 MB | EMDB map data format | |
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Header (meta data) | emd-42482-v30.xml emd-42482.xml | 17.5 KB 17.5 KB | Display Display | EMDB header |
Images | emd_42482.png | 66 KB | ||
Filedesc metadata | emd-42482.cif.gz | 5.7 KB | ||
Others | emd_42482_additional_1.map.gz emd_42482_half_map_1.map.gz emd_42482_half_map_2.map.gz | 10.6 MB 20.3 MB 20.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-42482 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-42482 | HTTPS FTP |
-Validation report
Summary document | emd_42482_validation.pdf.gz | 769 KB | Display | EMDB validaton report |
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Full document | emd_42482_full_validation.pdf.gz | 768.6 KB | Display | |
Data in XML | emd_42482_validation.xml.gz | 10 KB | Display | |
Data in CIF | emd_42482_validation.cif.gz | 11.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-42482 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-42482 | HTTPS FTP |
-Related structure data
Related structure data | 8ur5MC 8ur7C 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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Related items in Molecule of the Month |
-Map
File | Download / File: emd_42482.map.gz / Format: CCP4 / Size: 22.2 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.4281 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: #1
File | emd_42482_additional_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_42482_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_42482_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : I53_dn5 nanoparticle displaying the trimeric HA heads with heptad...
Entire | Name: I53_dn5 nanoparticle displaying the trimeric HA heads with heptad domain, TH-1heptad-I53_dn5 (local refinement of TH-1heptad) |
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Components |
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-Supramolecule #1: I53_dn5 nanoparticle displaying the trimeric HA heads with heptad...
Supramolecule | Name: I53_dn5 nanoparticle displaying the trimeric HA heads with heptad domain, TH-1heptad-I53_dn5 (local refinement of TH-1heptad) type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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-Supramolecule #2: Trimer head HA
Supramolecule | Name: Trimer head HA / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: synthetic construct (others) |
-Macromolecule #1: Trimer head HA,Hemagglutinin HA1 chain
Macromolecule | Name: Trimer head HA,Hemagglutinin HA1 chain / type: protein_or_peptide / ID: 1 / Details: I53_dn5 nanoparticle / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: synthetic construct (others) |
Molecular weight | Theoretical: 44.253539 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MDSKGSSQKG SRLLLLLVVS NLLLPQGVLA IAPLQLGNCS VAGWILGNPE CELLISKESW SYIVETPNPE NGTCFPGYFA DYEELRCQL SSVSSFERFE IFPKESSWPN HTVTGVSASC SHNGKSSFYR NLLWLTGKNG LYPNLSKSYV NNKEKEVLVL W GVHHPPNI ...String: MDSKGSSQKG SRLLLLLVVS NLLLPQGVLA IAPLQLGNCS VAGWILGNPE CELLISKESW SYIVETPNPE NGTCFPGYFA DYEELRCQL SSVSSFERFE IFPKESSWPN HTVTGVSASC SHNGKSSFYR NLLWLTGKNG LYPNLSKSYV NNKEKEVLVL W GVHHPPNI GNQRALYHTE NAYVLVVSSH YDRVFTPIIA KRPKVRDQEG RINYYWTLLE PGDTIIFEAN GNLIAPWYAF AL SRGFGSG SGSCIEHIEN EIAELAYLLG ELAYKLGEYR IAIRAYRIAL KSDPNNAEAW YNLGNAYYKQ GRYREAIEYY QKA LELDPN NAEAWYNLGN AYYERGEYEE AIEYYRKALR LDPNNADAMQ NLLNAKMREE GGWELQHHHH HH UniProtKB: Hemagglutinin |
-Macromolecule #2: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 2 / Number of copies: 12 / 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: 8 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS GLACIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 200 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: 0.5 µm |
-Image processing
Startup model | Type of model: OTHER / Details: cryoSPARC ab initio |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 690491 |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |