[English] 日本語
Yorodumi
- EMDB-12544: Hantaan virus-like particle glycoprotein spike in complex with Fa... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-12544
TitleHantaan virus-like particle glycoprotein spike in complex with Fab fragment HTN-Gn1.
Map dataA reconstruction of a Hantaan virus-like particle glycoprotein spike bound to the Fab fragment of HTN-Gn1.
Sample
  • Virus: Hantaan orthohantavirus
    • Protein or peptide: Fab fragment HTN-Gn1 Heavy chain
    • Protein or peptide: Fab fragment HTN-Gn1 Light chain
    • Protein or peptide: Envelope polyprotein
Function / homology
Function and homology information


: / symbiont-mediated suppression of host TRAF-mediated signal transduction / host cell Golgi membrane / host cell mitochondrion / host cell surface / host cell endoplasmic reticulum membrane / virion membrane / signal transduction / membrane / metal ion binding
Similarity search - Function
: / Hantavirus glycoprotein Gn, base / Hantavirus glycoprotein Gn / ITAM motif, hantavirus type / Envelope glycoprotein precursor, Hantavirus / Hantavirus glycoprotein Gn, head / Hantavirus ITAM motif / ITAM motif hantavirus type profile. / : / Hantavirus glycoprotein Gc, C-terminal ...: / Hantavirus glycoprotein Gn, base / Hantavirus glycoprotein Gn / ITAM motif, hantavirus type / Envelope glycoprotein precursor, Hantavirus / Hantavirus glycoprotein Gn, head / Hantavirus ITAM motif / ITAM motif hantavirus type profile. / : / Hantavirus glycoprotein Gc, C-terminal / Hantavirus glycoprotein Gc / Hantavirus glycoprotein Gc, N-terminal
Similarity search - Domain/homology
Envelopment polyprotein
Similarity search - Component
Biological speciesOryctolagus cuniculus (rabbit) / Hantaan orthohantavirus
Methodsubtomogram averaging / cryo EM / Resolution: 19.0 Å
AuthorsStass R / Rissanen I / Bowden TA / Huiskonen JT
Funding support United Kingdom, 1 items
OrganizationGrant numberCountry
European Research Council (ERC)649053 United Kingdom
CitationJournal: mBio / Year: 2021
Title: Structural Basis for a Neutralizing Antibody Response Elicited by a Recombinant Hantaan Virus Gn Immunogen.
Authors: Ilona Rissanen / Stefanie A Krumm / Robert Stass / Annalis Whitaker / James E Voss / Emily A Bruce / Sylvia Rothenberger / Stefan Kunz / Dennis R Burton / Juha T Huiskonen / Jason W Botten / ...Authors: Ilona Rissanen / Stefanie A Krumm / Robert Stass / Annalis Whitaker / James E Voss / Emily A Bruce / Sylvia Rothenberger / Stefan Kunz / Dennis R Burton / Juha T Huiskonen / Jason W Botten / Thomas A Bowden / Katie J Doores /
Abstract: Hantaviruses are a group of emerging pathogens capable of causing severe disease upon zoonotic transmission to humans. The mature hantavirus surface presents higher-order tetrameric assemblies of two ...Hantaviruses are a group of emerging pathogens capable of causing severe disease upon zoonotic transmission to humans. The mature hantavirus surface presents higher-order tetrameric assemblies of two glycoproteins, Gn and Gc, which are responsible for negotiating host cell entry and constitute key therapeutic targets. Here, we demonstrate that recombinantly derived Gn from Hantaan virus (HTNV) elicits a neutralizing antibody response (serum dilution that inhibits 50% infection [ID], 1:200 to 1:850) in an animal model. Using antigen-specific B cell sorting, we isolated monoclonal antibodies (mAbs) exhibiting neutralizing and non-neutralizing activity, termed mAb HTN-Gn1 and mAb nnHTN-Gn2, respectively. Crystallographic analysis reveals that these mAbs target spatially distinct epitopes at disparate sites of the N-terminal region of the HTNV Gn ectodomain. Epitope mapping onto a model of the higher order (Gn-Gc) spike supports the immune accessibility of the mAb HTN-Gn1 epitope, a hypothesis confirmed by electron cryo-tomography of the antibody with virus-like particles. These data define natively exposed regions of the hantaviral Gn that can be targeted in immunogen design. The spillover of pathogenic hantaviruses from rodent reservoirs into the human population poses a continued threat to human health. Here, we show that a recombinant form of the Hantaan virus (HTNV) surface-displayed glycoprotein, Gn, elicits a neutralizing antibody response in rabbits. We isolated a neutralizing (HTN-Gn1) and a non-neutralizing (nnHTN-Gn2) monoclonal antibody and provide the first molecular-level insights into how the Gn glycoprotein may be targeted by the antibody-mediated immune response. These findings may guide rational vaccine design approaches focused on targeting the hantavirus glycoprotein envelope.
History
DepositionMar 3, 2021-
Header (metadata) releaseJun 23, 2021-
Map releaseJun 23, 2021-
UpdateSep 15, 2021-
Current statusSep 15, 2021Processing site: PDBe / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 1.35
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by height
  • Surface level: 1.35
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-7nrh
  • Surface level: 1.35
  • Imaged by UCSF Chimera
  • Download
  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-7nrh
  • Imaged by Jmol
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_12544.png

Downloads & links

-
Map

FileDownload / File: emd_12544.map.gz / Format: CCP4 / Size: 931.6 KB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationA reconstruction of a Hantaan virus-like particle glycoprotein spike bound to the Fab fragment of HTN-Gn1.
Voxel sizeX=Y=Z: 7.04 Å
Density
Contour LevelBy AUTHOR: 1.35 / Movie #1: 1.35
Minimum - Maximum-5.8255186 - 8.464707
Average (Standard dev.)-0.1933619 (±0.8838172)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions626262
Spacing626262
CellA=B=C: 436.48 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z7.047.047.04
M x/y/z626262
origin x/y/z0.0000.0000.000
length x/y/z436.480436.480436.480
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS626262
D min/max/mean-5.8268.465-0.193

-
Supplemental data

-
Mask #1

Fileemd_12544_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Half map (odd) used to estimate resolution by FSC.

Fileemd_12544_half_map_1.map
AnnotationHalf map (odd) used to estimate resolution by FSC.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Half map (even) used to estimate resolution by FSC.

Fileemd_12544_half_map_2.map
AnnotationHalf map (even) used to estimate resolution by FSC.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Hantaan orthohantavirus

EntireName: Hantaan orthohantavirus
Components
  • Virus: Hantaan orthohantavirus
    • Protein or peptide: Fab fragment HTN-Gn1 Heavy chain
    • Protein or peptide: Fab fragment HTN-Gn1 Light chain
    • Protein or peptide: Envelope polyprotein

-
Supramolecule #1: Hantaan orthohantavirus

SupramoleculeName: Hantaan orthohantavirus / type: virus / ID: 1 / Parent: 0 / Macromolecule list: all / NCBI-ID: 1980471 / Sci species name: Hantaan orthohantavirus / Virus type: VIRUS-LIKE PARTICLE / Virus isolate: SPECIES / Virus enveloped: Yes / Virus empty: Yes
Host systemOrganism: Homo sapiens (human)

-
Macromolecule #1: Fab fragment HTN-Gn1 Heavy chain

MacromoleculeName: Fab fragment HTN-Gn1 Heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Oryctolagus cuniculus (rabbit)
Molecular weightTheoretical: 24.284264 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: TGQSLVESGG DLVKPEGSLT LTCTASGFSF SSTHWICWVR QAPGKGLEWI ACIYVGNTYD SYYANWAKGR FTISKTSSTT VTLQMTTLT AADTATYFCA RSGSVFGVVS LWGPGTLVTV SSGQPKAPSV FPLAPCCGDT PSSTVTLGCL VKGYLPEPVT V TWNSGTLT ...String:
TGQSLVESGG DLVKPEGSLT LTCTASGFSF SSTHWICWVR QAPGKGLEWI ACIYVGNTYD SYYANWAKGR FTISKTSSTT VTLQMTTLT AADTATYFCA RSGSVFGVVS LWGPGTLVTV SSGQPKAPSV FPLAPCCGDT PSSTVTLGCL VKGYLPEPVT V TWNSGTLT NGVRTFPSVR QSSGLYSLSS VVSVTSSSQP VTCNVAHPAT NTKVDKTVAP STCSGTKHHH HHH

-
Macromolecule #2: Fab fragment HTN-Gn1 Light chain

MacromoleculeName: Fab fragment HTN-Gn1 Light chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Oryctolagus cuniculus (rabbit)
Molecular weightTheoretical: 22.943162 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: TGQVLTQTPA SVSEPVEGTV TIKCQASQSI NNWLSWYQQR PGQPPKLLIY DASTVASGVS SRFKGSGSGT EFTLTISDLE CADAATYAC QSYGYGISIT DNSAFGGGTE VVVRGDPVAP SVLIFPPAAD QVATGTVTIV CVANKYFPDV TVTWEVDGTT Q TTGIENSK ...String:
TGQVLTQTPA SVSEPVEGTV TIKCQASQSI NNWLSWYQQR PGQPPKLLIY DASTVASGVS SRFKGSGSGT EFTLTISDLE CADAATYAC QSYGYGISIT DNSAFGGGTE VVVRGDPVAP SVLIFPPAAD QVATGTVTIV CVANKYFPDV TVTWEVDGTT Q TTGIENSK TPQNSADCTY NLSSTLTLTS TQYNSHKEYT CKVTQGTTSV VQSFNRGDC

-
Macromolecule #3: Envelope polyprotein

MacromoleculeName: Envelope polyprotein / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Hantaan orthohantavirus
Molecular weightTheoretical: 40.350871 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: TGSLRNVYDM KIECPHTVSF GENSVIGYVE LPPMPLADTA QMVPESSCSM DNHQSINTIT KYTQVIWRGK ADPGQSSQNS FETVSTEVD LKGTCVLKHK MVEESYRSRK SITCYDLSCN STFCKPTLYM IVPIHACNMM KSCLIALGPY RVQVVYERTY C MTGVLIEG ...String:
TGSLRNVYDM KIECPHTVSF GENSVIGYVE LPPMPLADTA QMVPESSCSM DNHQSINTIT KYTQVIWRGK ADPGQSSQNS FETVSTEVD LKGTCVLKHK MVEESYRSRK SITCYDLSCN STFCKPTLYM IVPIHACNMM KSCLIALGPY RVQVVYERTY C MTGVLIEG KCFVPDQSVV SIIKHGIFDI ASVHVVCFFV AVKGNTYKLF EQVKKSFEST CNDTENKVQG YYICIVGGNS AP IYVPTLD DFRSMEAFTG IFKSPHGEDH DLAGEEIASY SIVGPANAKV PHSASSDTLS LIAYSGIPSY SSLSILTSST DAK HVFSPG LFPKLNHTNC DKSAIPLTWT GMIDLPGYYE GTKHHHHHH

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsubtomogram averaging
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5 / Details: PBS
VitrificationCryogen name: ETHANE-PROPANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 4.77 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

ExtractionNumber tomograms: 42 / Number images used: 34460
Final angle assignmentType: PROJECTION MATCHING
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 19.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: Dynamo / Number subtomograms used: 2380
FSC plot (resolution estimation)

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more