[English] 日本語
Yorodumi
- PDB-6vx4: Density-fitted Model Structure of Antibody Variable Domains of Ty... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6vx4
TitleDensity-fitted Model Structure of Antibody Variable Domains of TyTx11 in Complex with Typhoid Toxin
Components
  • Cytolethal distending toxin subunit B
  • Pertussis like toxin subunit B
  • Pertussis toxin-like subunit ArtA
  • Variable Domain of Heavy Chain of Antibody TyTx11
  • Variable Domain of Kappa Chain of TyTx11 Antibody
KeywordsTOXIN / Typhoid Toxin / A2B5 / Antibody / Fab
Function / homology
Function and homology information


NAD+ ADP-ribosyltransferase activity / Transferases; Glycosyltransferases; Pentosyltransferases / : / toxin activity / endonuclease activity / Hydrolases; Acting on ester bonds / hydrolase activity / extracellular region
Similarity search - Function
Cytolethal distending toxin B / Bordetella pertussis toxin A / Pertussis toxin, subunit 1 / Bordetella pertussis toxin B, subunit 2/3, C-terminal / Pertussis toxin, subunit 2 and 3, C-terminal domain / Endonuclease/exonuclease/phosphatase / Endonuclease/Exonuclease/phosphatase family / Enterotoxin / Endonuclease/exonuclease/phosphatase superfamily / Prokaryotic membrane lipoprotein lipid attachment site profile.
Similarity search - Domain/homology
Pertussis like toxin subunit B / Pertussis-like toxin subunit ArtA / Cytolethal distending toxin S-CDT / Pertussis-like toxin subunit / Pertussis toxin-like subunit ArtA / Cytolethal distending toxin subunit B homolog
Similarity search - Component
Biological speciesMus musculus (house mouse)
Salmonella enterica subsp. enterica serovar Typhi str. CT18 (bacteria)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.12 Å
AuthorsNguyen, T. / Song, J.
Funding support United States, 3items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R03 AI135767 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R01 GM098621 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R01 GM116942 United States
CitationJournal: iScience / Year: 2021
Title: Mechanisms of typhoid toxin neutralization by antibodies targeting glycan receptor binding and nuclease subunits.
Authors: Changhwan Ahn / Yi-An Yang / Durga P Neupane / Tri Nguyen / Angelene F Richards / Ji Hyun Sim / Nicholas J Mantis / Jeongmin Song /
Abstract: Nearly all clinical isolates of Typhi, the cause of typhoid fever, are antibiotic resistant. All Typhi isolates secrete an AB exotoxin called typhoid toxin to benefit the pathogen during infection. ...Nearly all clinical isolates of Typhi, the cause of typhoid fever, are antibiotic resistant. All Typhi isolates secrete an AB exotoxin called typhoid toxin to benefit the pathogen during infection. Here, we demonstrate that antibiotic-resistant Typhi secretes typhoid toxin continuously during infection regardless of antibiotic treatment. We characterize typhoid toxin antibodies targeting glycan-receptor-binding PltB or nuclease CdtB, which neutralize typhoid toxin and , as demonstrated by using typhoid toxin secreted by antibiotic-resistant Typhi during human cell infection and lethal dose typhoid toxin challenge to mice. TyTx11 generated in this study neutralizes typhoid toxin effectively, comparable to TyTx4 that binds to all PltB subunits available per holotoxin. Cryoelectron microscopy explains that the binding of TyTx11 to CdtB makes this subunit inactive through CdtB catalytic-site conformational change. The identified toxin-neutralizing epitopes are conserved across all Typhi clinical isolates, offering critical insights into typhoid toxin-neutralizing strategies.
History
DepositionFeb 21, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 24, 2021Provider: repository / Type: Initial release
Revision 1.1May 5, 2021Group: Database references / Category: citation / Item: _citation.pdbx_database_id_DOI / _citation.title
Revision 1.2Jul 14, 2021Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.name

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-21429
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
K: Variable Domain of Kappa Chain of TyTx11 Antibody
C: Pertussis like toxin subunit B
H: Variable Domain of Heavy Chain of Antibody TyTx11
A: Pertussis like toxin subunit B
B: Pertussis like toxin subunit B
D: Pertussis like toxin subunit B
E: Pertussis like toxin subunit B
G: Pertussis toxin-like subunit ArtA
F: Cytolethal distending toxin subunit B


Theoretical massNumber of molelcules
Total (without water)147,8229
Polymers147,8229
Non-polymers00
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

#1: Antibody Variable Domain of Kappa Chain of TyTx11 Antibody


Mass: 11689.935 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Cell: Hybridoma / Cell line (production host): Hybridoma / Production host: Mus musculus (house mouse)
#2: Protein
Pertussis like toxin subunit B / Subtilase cytotoxin subunit B


Mass: 12563.042 Da / Num. of mol.: 5
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Salmonella enterica subsp. enterica serovar Typhi str. CT18 (bacteria)
Gene: pltB, D4F19_07865, D4F39_13740, D4G09_02615, D4X81_03235, D5848_06295, D5891_16360, D5B50_14740, D5C10_10475, D6331_06440, D6K86_15515, D6P24_09080, D6Q71_07195, D7N07_01470, D8R98_02600, D8S38_ ...Gene: pltB, D4F19_07865, D4F39_13740, D4G09_02615, D4X81_03235, D5848_06295, D5891_16360, D5B50_14740, D5C10_10475, D6331_06440, D6K86_15515, D6P24_09080, D6Q71_07195, D7N07_01470, D8R98_02600, D8S38_09485, DL104_04040, DLF44_02615, DM364_15630, DMA85_08120, DMV05_17400, DN022_06665, DN116_07470, DN223_02675, DNJ32_13915, DNL67_05455, DNM39_02515, DNV82_15785, DNV95_15160, DOH59_08615, DP757_14390, DPC06_03915, DPJ15_14935, DPS97_10830, DQ802_09840, DQD72_07750, DQJ57_09285, DRE79_02610, DRW87_14355, DRX58_02590, DRX79_07315, DS260_02735, DS269_05775, DS339_07525, DS529_00005, DSM93_00460, DST18_05335, DTV88_06700, DU090_09370, DUQ83_10880, DUW14_00135, DVF55_05015, EDK96_01785, EIT32_03595, EIT43_00570, YL55_10165
Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: A0A286LNT9, UniProt: Q8Z6A3*PLUS
#3: Antibody Variable Domain of Heavy Chain of Antibody TyTx11


Mass: 20049.723 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Cell line: Hybridoma / Cell line (production host): Hybridoma / Production host: Mus musculus (house mouse)
#4: Protein Pertussis toxin-like subunit ArtA / / Pertussis-like toxin subunit ArtA


Mass: 25117.145 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Salmonella enterica subsp. enterica serovar Typhi str. CT18 (bacteria)
Gene: artA, CIJ14_23170, D4382_23660, D4E24_23260, D4Y21_22940, D5806_21720, D6Q50_22735, D9Q66_22850, DJ817_22925, DJ902_22835, DKA33_22665, DOG98_22205, DP807_22355, DPD01_22815, DPO73_22750, DQ973_ ...Gene: artA, CIJ14_23170, D4382_23660, D4E24_23260, D4Y21_22940, D5806_21720, D6Q50_22735, D9Q66_22850, DJ817_22925, DJ902_22835, DKA33_22665, DOG98_22205, DP807_22355, DPD01_22815, DPO73_22750, DQ973_22620, DQC14_23005, DQC85_22640, DQS90_22840, EDL32_22840, EGM32_22620, EIW71_22495, PltA
Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: A0A3Z7CEY9, UniProt: Q8Z6A4*PLUS
#5: Protein Cytolethal distending toxin subunit B / Cytolethal distending toxin subunit B family protein / Cytolethal distending toxin subunit CdtB


Mass: 28149.777 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Salmonella enterica subsp. enterica serovar Typhi str. CT18 (bacteria)
Gene: cdtB, ABO08_07050, ACK79_04015, ACS18_04320, ADQ64_04510, AF726_04075, AG53_02460, AH360_09375, AH874_08650, AHN91_05150, AHS86_01310, AHX56_04670, AHY46_21185, AIA22_01750, AID13_25040, ALX58_ ...Gene: cdtB, ABO08_07050, ACK79_04015, ACS18_04320, ADQ64_04510, AF726_04075, AG53_02460, AH360_09375, AH874_08650, AHN91_05150, AHS86_01310, AHX56_04670, AHY46_21185, AIA22_01750, AID13_25040, ALX58_21685, AU833_04405, AU920_00110, AXO05_06525, BXD49_09845, BXO48_02100, C3O10_15300, CIJ14_23185, D4382_23675, D4E01_03970, D4E24_23275, D4E82_03815, D4X65_01210, D4Y21_22955, D4Y61_01580, D5769_01120, D5773_04415, D5806_21735, D5905_00655, D5938_05180, D5A94_07255, D5B66_02920, D5P52_03820, D5W53_03345, D5X56_14350, D6J84_12220, D6Q32_04050, D6Q48_23450, D6Q50_22750, D6R14_01875, D6S47_01810, D6S52_04640, D7M89_03925, D7O59_01230, D8Q95_07260, D8R18_22625, D8R28_03780, D8R78_05465, D8S31_11805, D9P30_01530, D9P43_07260, D9Q66_22865, DAX91_01380, DJ817_22940, DJ902_22850, DK094_15420, DK681_22625, DK719_00065, DKA33_22680, DKS84_01205, DKT00_12650, DL111_03690, DLB36_01945, DLC21_01190, DM347_00605, DM358_02585, DMA89_03440, DML97_01185, DMM24_06680, DMU80_01195, DMU94_00450, DMV34_24005, DN115_03160, DN181_02750, DN218_09840, DN257_00960, DNM18_03225, DNP18_20975, DNU33_00605, DNU46_06990, DNV11_08545, DNV24_09060, DNV84_01240, DNZ24_19360, DNZ91_01190, DO736_07435, DO994_18310, DOA32_23160, DOC12_13865, DOC15_02915, DOC34_02235, DOG98_22220, DOH12_03665, DOQ73_02885, DOR42_02915, DOR52_05945, DOW79_02275, DOX21_23175, DP728_08755, DP748_00630, DP792_04070, DP807_22370, DP838_14200, DPC30_05570, DPD01_22830, DPD54_23140, DPE66_01635, DPE90_12380, DPJ07_11775, DPK35_02680, DPO73_22765, DPR96_19355, DPS68_01210, DPT88_22945, DPZ91_06800, DQ837_03030, DQ973_22635, DQ986_03355, DQC14_23020, DQC85_22655, DQJ66_20360, DQJ71_17745, DQK72_01185, DQR07_01185, DQS17_02890, DQS90_22855, DQY62_02055, DQZ13_01205, DRA30_01205, DRF26_01185, DRK15_02285, DRK71_19590, DRK91_13535, DRL63_05765, DRM75_04210, DRT15_23155, DRU74_02985, DRV60_04480, DRX43_08215, DRY73_10160, DRZ18_10315, DS251_02230, DS368_09485, DS470_09640, DS570_05080, DS689_07420, DSA82_02305, DSA99_17640, DSF62_00555, DSQ94_23515, DTE82_23795, DTF17_02235, DTF39_05055, DTG02_04520, DTG24_03875, DTG49_09625, DTG90_25155, DTH05_08145, DTT89_00540, DTU25_03425, DTW06_03295, DU078_23475, DU168_00610, DU852_01200, DU949_19355, DUA52_03235, DUC30_24990, DUE02_01595, DUP59_10365, DUQ37_03210, DUQ73_01530, DUR82_01195, DUR89_07585, DUU35_01075, DUU43_23100, DUU47_01595, DUV63_05900, DVF01_11150, EBC34_19090, EBC39_01055, ECA57_07075, ED432_03555, EDL32_22855, EGM22_03890, EGM32_22635, EHB26_00195, EHD17_22415, EHF16_02745, EIW64_10595, EIW71_22510, EIW76_01180, GX90_01205, JF03_03615, KO25_07020, LB54_02820, NCTC8272_01874, QC88_03775, R126_05570, R133_02035, RY52_03905, YR14_00925, ZG82_07355
Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: A0A447PE99, UniProt: Q8Z6A7*PLUS, Hydrolases; Acting on ester bonds

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

Component
IDNameTypeDetailsEntity IDParent-IDSource
1Complex of TyTx11 Fab with Typhoid toxinCOMPLEXMap of Fab segment of IgG antibody TyTx11 in complex with purified Typhoid toxinall0MULTIPLE SOURCES
2Typhoid toxinCOMPLEXS. Typhi A2B5 toxin wild type#2, #4-#51RECOMBINANT
3TyTx11 FabCOMPLEXFab segment of IgG antibody TyTx11#1, #31RECOMBINANT
Molecular weight
IDEntity assembly-IDExperimental value
11NO
21NO
13
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
12Salmonella enterica subsp. enterica serovar Typhi str. CT18 (bacteria)220341
23Mus musculus (house mouse)10090
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-IDCell
12Escherichia coli BL21(DE3) (bacteria)469008
23Mus musculus (house mouse)10090Hybridoma
Buffer solutionpH: 7.5
Buffer component
IDConc.NameFormulaBuffer-ID
115 mMtris(hydroxymethyl)aminomethaneTris1
2150 mMsodium chlorideNaClSodium chloride1
SpecimenConc.: 0.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Details: Freshly prepared size-exclusion-chromatography purified complex of TyTx11 IgG and Typhoid toxin wild-type
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K / Details: blot for 2.0 second before plunging

-
Electron microscopy imaging

Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company
MicroscopyModel: FEI TALOS ARCTICA
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy / Nominal magnification: 63000 X / Nominal defocus max: 1500 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm
Specimen holderCryogen: NITROGEN
Image recordingElectron dose: 54.7 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)
EM imaging opticsEnergyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV

-
Processing

SoftwareName: PHENIX / Version: dev_3765: / Classification: refinement
EM software
IDNameVersionCategory
2EPUimage acquisition
4GctfCTF correction
7Coot0.8.9.1model fitting
12RELION3.13D reconstruction
13PHENIX1.16-3549model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 3.12 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 61478 / Symmetry type: POINT
Atomic model buildingDetails: Initial local fitting was done using Chimera and then Coot was used for rebuilding Fab variable domains into correct sequences. Refinement was performed using Real Space Refine in PHENIX and ...Details: Initial local fitting was done using Chimera and then Coot was used for rebuilding Fab variable domains into correct sequences. Refinement was performed using Real Space Refine in PHENIX and was iterated with manual building in Coot.
Atomic model building
IDPDB-IDPdb chain-ID 3D fitting-ID
14K6L

4k6l

1
26GFF

6gff

K1
31F11

1f11

B1
41
51
61
71
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00210059
ELECTRON MICROSCOPYf_angle_d0.39813702
ELECTRON MICROSCOPYf_dihedral_angle_d3.3671377
ELECTRON MICROSCOPYf_chiral_restr0.0421521
ELECTRON MICROSCOPYf_plane_restr0.0021756

+
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