[English] 日本語
Yorodumi
- EMDB-9828: The cryo-EM structure of HAV bound to a neutralizing antibody-F6 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-9828
TitleThe cryo-EM structure of HAV bound to a neutralizing antibody-F6
Map datamap of F6_Fab_HAV complex
Sample
  • Complex: Human hepatitis A virus and antibody-F6
    • Complex: antibody-F6
      • Protein or peptide: FAB Light Chain
      • Protein or peptide: FAB Heavy Chain
    • Virus: Human hepatitis A virus
      • Protein or peptide: VP1
      • Protein or peptide: VP2
      • Protein or peptide: VP3
KeywordsIcosahedral symmetry / neutralizing antibody / HAV / complex / VIRUS
Function / homology
Function and homology information


host cell mitochondrial outer membrane / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / picornain 3C / ribonucleoside triphosphate phosphatase activity / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / host multivesicular body / nucleoside-triphosphate phosphatase / channel activity / monoatomic ion transmembrane transport ...host cell mitochondrial outer membrane / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / picornain 3C / ribonucleoside triphosphate phosphatase activity / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / host multivesicular body / nucleoside-triphosphate phosphatase / channel activity / monoatomic ion transmembrane transport / RNA helicase activity / symbiont entry into host cell / RNA-directed RNA polymerase / viral RNA genome replication / cysteine-type endopeptidase activity / RNA-dependent RNA polymerase activity / virus-mediated perturbation of host defense response / DNA-templated transcription / virion attachment to host cell / structural molecule activity / proteolysis / RNA binding / ATP binding / membrane
Similarity search - Function
Hepatitis A virus, protein VP1-2A / : / Hepatitis A virus viral protein VP / 2B protein soluble domain / Helicase/polymerase/peptidase polyprotein, Calicivirus-type / Peptidase C3A/C3B, picornaviral / 3C cysteine protease (picornain 3C) / Picornavirales 3C/3C-like protease domain / Picornavirales 3C/3C-like protease domain profile. / Picornavirus capsid ...Hepatitis A virus, protein VP1-2A / : / Hepatitis A virus viral protein VP / 2B protein soluble domain / Helicase/polymerase/peptidase polyprotein, Calicivirus-type / Peptidase C3A/C3B, picornaviral / 3C cysteine protease (picornain 3C) / Picornavirales 3C/3C-like protease domain / Picornavirales 3C/3C-like protease domain profile. / Picornavirus capsid / picornavirus capsid protein / Helicase, superfamily 3, single-stranded RNA virus / Superfamily 3 helicase of positive ssRNA viruses domain profile. / Helicase, superfamily 3, single-stranded DNA/RNA virus / RNA helicase / Picornavirus/Calicivirus coat protein / Viral coat protein subunit / RNA-directed RNA polymerase, C-terminal domain / Viral RNA-dependent RNA polymerase / Reverse transcriptase/Diguanylate cyclase domain / RNA-directed RNA polymerase, catalytic domain / RdRp of positive ssRNA viruses catalytic domain profile. / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan / DNA/RNA polymerase superfamily
Similarity search - Domain/homology
Biological speciesMus musculus (house mouse) / Human hepatitis A virus Hu/Australia/HM175/1976 / Human hepatitis A virus
Methodsingle particle reconstruction / cryo EM / Resolution: 3.68 Å
AuthorsCao L / Liu P
Funding support China, 3 items
OrganizationGrant numberCountry
National Science Foundation (China)31570717 China
National Science Foundation (China)31800145 China
National Science Foundation (China)31370735 China
CitationJournal: PLoS Biol / Year: 2019
Title: Structural basis for neutralization of hepatitis A virus informs a rational design of highly potent inhibitors.
Authors: Lei Cao / Pi Liu / Pan Yang / Qiang Gao / Hong Li / Yao Sun / Ling Zhu / Jianping Lin / Dan Su / Zihe Rao / Xiangxi Wang /
Abstract: Hepatitis A virus (HAV), an enigmatic and ancient pathogen, is a major causative agent of acute viral hepatitis worldwide. Although there are effective vaccines, antivirals against HAV infection are ...Hepatitis A virus (HAV), an enigmatic and ancient pathogen, is a major causative agent of acute viral hepatitis worldwide. Although there are effective vaccines, antivirals against HAV infection are still required, especially during fulminant hepatitis outbreaks. A more in-depth understanding of the antigenic characteristics of HAV and the mechanisms of neutralization could aid in the development of rationally designed antiviral drugs targeting HAV. In this paper, 4 new antibodies-F4, F6, F7, and F9-are reported that potently neutralize HAV at 50% neutralizing concentration values (neut50) ranging from 0.1 nM to 0.85 nM. High-resolution cryo-electron microscopy (cryo-EM) structures of HAV bound to F4, F6, F7, and F9, together with results of our previous studies on R10 fragment of antigen binding (Fab)-HAV complex, shed light on the locations and nature of the epitopes recognized by the 5 neutralizing monoclonal antibodies (NAbs). All the epitopes locate within the same patch and are highly conserved. The key structure-activity correlates based on the antigenic sites have been established. Based on the structural data of the single conserved antigenic site and key structure-activity correlates, one promising drug candidate named golvatinib was identified by in silico docking studies. Cell-based antiviral assays confirmed that golvatinib is capable of blocking HAV infection effectively with a 50% inhibitory concentration (IC50) of approximately 1 μM. These results suggest that the single conserved antigenic site from complete HAV capsid is a good antiviral target and that golvatinib could function as a lead compound for anti-HAV drug development.
History
DepositionFeb 18, 2019-
Header (metadata) releaseMar 18, 2020-
Map releaseMar 18, 2020-
UpdateOct 23, 2024-
Current statusOct 23, 2024Processing site: PDBj / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.008
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by radius
  • Surface level: 0.008
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-6jhr
  • Surface level: 0.008
  • Imaged by UCSF Chimera
  • Download
  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-6jhr
  • Imaged by Jmol
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_9828.png

Downloads & links

-
Map

FileDownload / File: emd_9828.map.gz / Format: CCP4 / Size: 193.2 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationmap of F6_Fab_HAV complex
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.35 Å/pix.
x 370 pix.
= 499.5 Å		1.35 Å/pix.
x 370 pix.
= 499.5 Å		1.35 Å/pix.
x 370 pix.
= 499.5 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.35 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.006 / Movie #1: 0.008
Minimum - Maximum-0.037005812 - 0.0940222
Average (Standard dev.)0.000719891 (±0.0063448227)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin-186-186-186
Dimensions370370370
Spacing370370370
CellA=B=C: 499.5 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.351.351.35
M x/y/z370370370
origin x/y/z0.0000.0000.000
length x/y/z499.500499.500499.500
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS-186-186-186
NC/NR/NS370370370
D min/max/mean-0.0370.0940.001

-
Supplemental data

-
Sample components

-
Entire : Human hepatitis A virus and antibody-F6

EntireName: Human hepatitis A virus and antibody-F6
Components
  • Complex: Human hepatitis A virus and antibody-F6
    • Complex: antibody-F6
      • Protein or peptide: FAB Light Chain
      • Protein or peptide: FAB Heavy Chain
    • Virus: Human hepatitis A virus
      • Protein or peptide: VP1
      • Protein or peptide: VP2
      • Protein or peptide: VP3

-
Supramolecule #1: Human hepatitis A virus and antibody-F6

SupramoleculeName: Human hepatitis A virus and antibody-F6 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all

-
Supramolecule #3: antibody-F6

SupramoleculeName: antibody-F6 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #4-#5
Source (natural)Organism: Mus musculus (house mouse)

-
Supramolecule #2: Human hepatitis A virus

SupramoleculeName: Human hepatitis A virus / type: virus / ID: 2 / Parent: 1 / Macromolecule list: #1-#3 / NCBI-ID: 208726 / Sci species name: Human hepatitis A virus / Virus type: VIRION / Virus isolate: STRAIN / Virus enveloped: No / Virus empty: No

-
Macromolecule #1: VP1

MacromoleculeName: VP1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Human hepatitis A virus Hu/Australia/HM175/1976
Molecular weightTheoretical: 30.820629 KDa
SequenceString: VGDDSGGFST TVSTEQNVPD PQVGITTMRD LKGKANRGKM DVSGVQAPVG AITTIEDPVL AKKVPETFPE LKPGESRHTS DHMSIYKFM GRSHFLCTFT FNSNNKEYTF PITLSSTSNP PHGLPSTLRW FFNLFQLYRG PLDLTIIITG ATDVDGMAWF T PVGLAVDT ...String:
VGDDSGGFST TVSTEQNVPD PQVGITTMRD LKGKANRGKM DVSGVQAPVG AITTIEDPVL AKKVPETFPE LKPGESRHTS DHMSIYKFM GRSHFLCTFT FNSNNKEYTF PITLSSTSNP PHGLPSTLRW FFNLFQLYRG PLDLTIIITG ATDVDGMAWF T PVGLAVDT PWVEKESALQ IDYKTALGAV RFNTRRTGNI QIRLPWYSYL YAVSGALDGL GDKTDSTFGL VSIQIANYNH SD EYLSFSC YLSVTEQSEF YFPRAPLNSN AMLSTESMMS R

-
Macromolecule #2: VP2

MacromoleculeName: VP2 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Human hepatitis A virus Hu/Australia/HM175/1976
Molecular weightTheoretical: 24.898172 KDa
SequenceString: DIEEEQMIQS VDRTAVTGAS YFTSVDQSSV HTAEVGSHQI EPLKTSVDKP GSKKTQGEKF FLIHSARWLT THALFHEVAK LDVVKLLYN EQFAVQGLLR YHTYARFGIE IQVQINPTPF QQGGLICAMV PGDQSYGSIA SLTVYPHGLL NCNINNVVRI K VPFIYTRG ...String:
DIEEEQMIQS VDRTAVTGAS YFTSVDQSSV HTAEVGSHQI EPLKTSVDKP GSKKTQGEKF FLIHSARWLT THALFHEVAK LDVVKLLYN EQFAVQGLLR YHTYARFGIE IQVQINPTPF QQGGLICAMV PGDQSYGSIA SLTVYPHGLL NCNINNVVRI K VPFIYTRG AYHFKDPQYP VWELTIRVWS ELNIGTGTSA YTSLNVLARF TDLELHGLTP LSTQ

-
Macromolecule #3: VP3

MacromoleculeName: VP3 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Human hepatitis A virus Hu/Australia/HM175/1976
Molecular weightTheoretical: 27.835693 KDa
SequenceString: MMRNETRVST TENVVNLSNY EDARAKMSFA LDQEDWKSDP SQGGGIKITH FTTWTSIPTL AAQFPFNASD SVGQQIKVIP VDPYFFQMT NTNPDQKCIT ALASICQMFC FWRGDLVFDF QVFPTKYHSG RLLFCFVPGN ELIDVTGITL KQATTAPCAV M DIAGVQST ...String:
MMRNETRVST TENVVNLSNY EDARAKMSFA LDQEDWKSDP SQGGGIKITH FTTWTSIPTL AAQFPFNASD SVGQQIKVIP VDPYFFQMT NTNPDQKCIT ALASICQMFC FWRGDLVFDF QVFPTKYHSG RLLFCFVPGN ELIDVTGITL KQATTAPCAV M DIAGVQST LRFRVPWISD TPYRVNRYTK EAHQKGEYTA IGKLIVYCYN RLTSPSNVAH HVRVNVYLSA INLECFAPLY HA MDVTTQ

-
Macromolecule #4: FAB Light Chain

MacromoleculeName: FAB Light Chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 23.788209 KDa
SequenceString: DIVLTQSPAI MSASPGERVT MTCSAHQYVS YMHWYQQKSG TSPKRWIYDT SRLADAIPQR FSGRGSGTSY SLTISSMEAE DAATYYCQQ WQSNPYTFGG GTKLEIKRAD AAPTVSIFPP SSEQLTSGGA SVVCFLNNFY PKDINVKWKI DGSERQNGVL N SWTDQDSK ...String:
DIVLTQSPAI MSASPGERVT MTCSAHQYVS YMHWYQQKSG TSPKRWIYDT SRLADAIPQR FSGRGSGTSY SLTISSMEAE DAATYYCQQ WQSNPYTFGG GTKLEIKRAD AAPTVSIFPP SSEQLTSGGA SVVCFLNNFY PKDINVKWKI DGSERQNGVL N SWTDQDSK DSTYSMSSTL TLTKDEYERH NSYTCEATHK TSTSPIVKSF NRNEC

-
Macromolecule #5: FAB Heavy Chain

MacromoleculeName: FAB Heavy Chain / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 24.208324 KDa
SequenceString: EVKLVESGGG LVKPGGSLKL SCAASMYNFQ HYGMSWVRQT PEKRLEWVAT IQTNATYTYY PDSVKGRFTI SRDNARNILY LQMSSLRSG DTAMYYCARR DNIECHYYFD YWGQGTTLTV SSPKTTPPSV YPLAPASAST AASMVTLGCL VKGYFPEPVT V TWNSGSLS ...String:
EVKLVESGGG LVKPGGSLKL SCAASMYNFQ HYGMSWVRQT PEKRLEWVAT IQTNATYTYY PDSVKGRFTI SRDNARNILY LQMSSLRSG DTAMYYCARR DNIECHYYFD YWGQGTTLTV SSPKTTPPSV YPLAPASAST AASMVTLGCL VKGYFPEPVT V TWNSGSLS SGVHTFPAVL QSDLYTLSSS VTVPSSTWPS ETVTCNVAHP ASSTKVDKKI VPR

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K2 BASE (4k x 4k) / Average electron dose: 1.3 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: EMDB MAP
EMDB ID:

6688

Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.68 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: PHENIX / Number images used: 7245
Initial angle assignmentType: RANDOM ASSIGNMENT
Final angle assignmentType: MAXIMUM LIKELIHOOD

+
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