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Yorodumi- EMDB-42485: I53_dn5 nanoparticle displaying the trimeric HA heads with heptad... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-42485 | |||||||||
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Title | I53_dn5 nanoparticle displaying the trimeric HA heads with heptad domain, TH-6heptad-I53_dn5 | |||||||||
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Sample |
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Keywords | Influenza virus / Hemagglutinin nanoparticle vaccine / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / VIRAL PROTEIN | |||||||||
Biological species | synthetic construct (others) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.0 Å | |||||||||
Authors | Park YJ / Veesler D | |||||||||
Funding support | United States, 2 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_42485.map.gz | 483.9 MB | EMDB map data format | |
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Header (meta data) | emd-42485-v30.xml emd-42485.xml | 18.1 KB 18.1 KB | Display Display | EMDB header |
Images | emd_42485.png | 76.7 KB | ||
Filedesc metadata | emd-42485.cif.gz | 5.1 KB | ||
Others | emd_42485_additional_1.map.gz emd_42485_half_map_1.map.gz emd_42485_half_map_2.map.gz | 255.6 MB 475.7 MB 475.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-42485 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-42485 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_42485.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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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_42485_additional_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_42485_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_42485_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-6heptad-I53_dn5 |
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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-6heptad-I53_dn5 type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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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) |
-Supramolecule #3: Pentamer
Supramolecule | Name: Pentamer / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: synthetic construct (others) |
-Macromolecule #1: Trimer head HA
Macromolecule | Name: Trimer head HA / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: synthetic construct (others) |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MDSKGSSQKG SRLLLLLVVS NLLLPQGVLA IAPLQLGNCS VAGWILGNPE CELLISKESW SYIVETPNPE NGTCFPGYFA DYEELRCQLS SVSSFERFEI FPKESSWPNH TVTGVSASCS HNGKSSFYRN LLWLTGKNGL YPNLSKSYVN NKEKEVLVLW GVHHPPNIGN ...String: MDSKGSSQKG SRLLLLLVVS NLLLPQGVLA IAPLQLGNCS VAGWILGNPE CELLISKESW SYIVETPNPE NGTCFPGYFA DYEELRCQLS SVSSFERFEI FPKESSWPNH TVTGVSASCS HNGKSSFYRN LLWLTGKNGL YPNLSKSYVN NKEKEVLVLW GVHHPPNIGN QRALYHTENA YVLVVSSHYD RVFTPIIAKR PKVRDQEGRI NYYWTLLEPG DTIIFEANGN LIAPWYAFAL SRGFGSGSGS CIENINSKIY HIEDKIEEIN RKIEHILSKI YHIERKIEEI LNEIAELAYL LGELAYKLGE YRIAIRAYRI ALKSDPNNAE AWYNLGNAYY KQGRYREAIE YYQKALELDP NNAEAWYNLG NAYYERGEYE EAIEYYRKAL RLDPNNADAM QNLLNAKMRE EGGWELQHHH HHH |
-Macromolecule #2: Pentamer
Macromolecule | Name: Pentamer / type: protein_or_peptide / ID: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: synthetic construct (others) |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MGKYDGSKLR IGILHARGNA EIILALVLGA LKRLQEFGVK RENIIIETVP GSFELPYGSK LFVEKQKRLG KPLDAIIPIG VLIRGSTPHF DYIADSTTHQ LMKLNFELGI PVIFGVITAD TDEQAEARAG LIEGKMHNHG EDWGAAAVEM ATKFNLEHHH HHH |
-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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Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.5 µm |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 60.0 e/Å2 |
-Image processing
Startup model | Type of model: OTHER / Details: cryoSPARC ab initio |
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Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 35947 |