[English] 日本語
Yorodumi
- PDB-8vdf: Cryo-EM structure of human monoclonal antibody C7 targeting IT4VA... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8vdf
TitleCryo-EM structure of human monoclonal antibody C7 targeting IT4VAR22 CIDRa1.7 (PfEMP1 A)
Components
  • C7 Fab heavy chain
  • C7 Fab lamda chain
  • Erythrocyte membrane protein 1
KeywordsIMMUNE SYSTEM / Malaria / PfEMP1 / Human monoclonal antibodies / Severe malaria.
Function / homology
Function and homology information


host cell surface receptor binding / membrane
Similarity search - Function
: / PfEMP1 protein, CIDRalpha1 domain / Plasmodium falciparum erythrocyte membrane protein-1, N-terminal segment / N-terminal segments of PfEMP1 / : / Cysteine-rich interdomain region 1 gamma / Cysteine-Rich Interdomain Region 1 gamma / Duffy-binding-like domain, C-terminal subdomain / Duffy-binding-like domain / PFEMP1 DBL domain ...: / PfEMP1 protein, CIDRalpha1 domain / Plasmodium falciparum erythrocyte membrane protein-1, N-terminal segment / N-terminal segments of PfEMP1 / : / Cysteine-rich interdomain region 1 gamma / Cysteine-Rich Interdomain Region 1 gamma / Duffy-binding-like domain, C-terminal subdomain / Duffy-binding-like domain / PFEMP1 DBL domain / Plasmodium falciparum erythrocyte membrane protein 1, acidic terminal segment superfamily / Plasmodium falciparum erythrocyte membrane protein 1, acidic terminal segment / acidic terminal segments, variant surface antigen of PfEMP1 / Duffy-antigen binding / Duffy-antigen binding superfamily / Duffy binding domain
Similarity search - Domain/homology
Erythrocyte membrane protein 1
Similarity search - Component
Biological speciesPlasmodium falciparum (malaria parasite P. falciparum)
Homo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å
AuthorsRaghavan, S.S.R. / Ward, A.B.
Funding support United States, Denmark, 2items
OrganizationGrant numberCountry
Bill & Melinda Gates Foundation United States
Lundbeckfonden Denmark
CitationJournal: Nature / Year: 2024
Title: Broadly inhibitory antibodies to severe malaria virulence proteins.
Authors: Raphael A Reyes / Sai Sundar Rajan Raghavan / Nicholas K Hurlburt / Viola Introini / Sebastiaan Bol / Ikhlaq Hussain Kana / Rasmus W Jensen / Elizabeth Martinez-Scholze / María Gestal-Mato ...Authors: Raphael A Reyes / Sai Sundar Rajan Raghavan / Nicholas K Hurlburt / Viola Introini / Sebastiaan Bol / Ikhlaq Hussain Kana / Rasmus W Jensen / Elizabeth Martinez-Scholze / María Gestal-Mato / Borja López-Gutiérrez / Silvia Sanz / Cristina Bancells / Monica Lisa Fernández-Quintero / Johannes R Loeffler / James Alexander Ferguson / Wen-Hsin Lee / Greg Michael Martin / Thor G Theander / John P A Lusingu / Daniel T R Minja / Isaac Ssewanyana / Margaret E Feeney / Bryan Greenhouse / Andrew B Ward / Maria Bernabeu / Marie Pancera / Louise Turner / Evelien M Bunnik / Thomas Lavstsen /
Abstract: Malaria pathology is driven by the accumulation of Plasmodium falciparum-infected erythrocytes in microvessels. This process is mediated by the polymorphic erythrocyte membrane protein 1 (PfEMP1) ...Malaria pathology is driven by the accumulation of Plasmodium falciparum-infected erythrocytes in microvessels. This process is mediated by the polymorphic erythrocyte membrane protein 1 (PfEMP1) adhesion proteins of the parasite. A subset of PfEMP1 variants that bind to human endothelial protein C receptor (EPCR) through their CIDRα1 domains is responsible for severe malaria pathogenesis. A longstanding question is whether individual antibodies can recognize the large repertoire of circulating PfEMP1 variants. Here we describe two broadly reactive and inhibitory human monoclonal antibodies to CIDRα1. The antibodies isolated from two different individuals exhibited similar and consistent EPCR-binding inhibition of diverse CIDRα1 domains, representing five of the six subclasses of CIDRα1. Both antibodies inhibited EPCR binding of both recombinant full-length and native PfEMP1 proteins, as well as parasite sequestration in bioengineered 3D human brain microvessels under physiologically relevant flow conditions. Structural analyses of the two antibodies in complex with three different CIDRα1 antigen variants reveal similar binding mechanisms that depend on interactions with three highly conserved amino acid residues of the EPCR-binding site in CIDRα1. These broadly reactive antibodies are likely to represent a common mechanism of acquired immunity to severe malaria and offer novel insights for the design of a vaccine or treatment targeting severe malaria.
History
DepositionDec 15, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 2, 2024Provider: repository / Type: Initial release
Revision 1.1Nov 6, 2024Group: Data collection / Structure summary
Category: em_admin / pdbx_entry_details / pdbx_modification_feature
Item: _em_admin.last_update
Revision 1.2Dec 4, 2024Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _em_admin.last_update
Revision 1.3Dec 18, 2024Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID / _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Erythrocyte membrane protein 1
H: C7 Fab heavy chain
L: C7 Fab lamda chain


Theoretical massNumber of molelcules
Total (without water)180,5173
Polymers180,5173
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

-
Components

#1: Protein Erythrocyte membrane protein 1


Mass: 133706.328 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Plasmodium falciparum (malaria parasite P. falciparum)
Gene: IT4_var22 / Cell line (production host): HiFi / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: A3R6S4
#2: Antibody C7 Fab heavy chain


Mass: 23871.637 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): expi CHO / Production host: Cricetulus griseus (Chinese hamster)
#3: Antibody C7 Fab lamda chain


Mass: 22939.492 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): expo CHO / Production host: Cricetulus griseus (Chinese hamster)
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: Plasmodium falciparum Erythrocyte Membrane Protein 1 complexed with human monoclonal antibody
Type: COMPLEX / Entity ID: all / Source: RECOMBINANT
Molecular weightValue: 190 kDa/nm / Experimental value: YES
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Cricetulus griseus (Chinese hamster)
Buffer solutionpH: 7.5
SpecimenConc.: 0.45 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: GOLD / Grid type: UltrAuFoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 90 % / Chamber temperature: 277 K

-
Electron microscopy imaging

MicroscopyModel: TFS GLACIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2200 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k)

-
Processing

CTF correctionType: PHASE FLIPPING ONLY
3D reconstructionResolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 80835 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0042640
ELECTRON MICROSCOPYf_angle_d0.8343559
ELECTRON MICROSCOPYf_dihedral_angle_d5.443348
ELECTRON MICROSCOPYf_chiral_restr0.05379
ELECTRON MICROSCOPYf_plane_restr0.006448

+
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