[English] 日本語
Yorodumi
- PDB-9n6e: L9-targeting immunogen bound to three copies of L9 Fab -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9n6e
TitleL9-targeting immunogen bound to three copies of L9 Fab
Components
  • L9 Fab heavy chain
  • L9 Fab light chain
  • L9-targeting immunogen
KeywordsIMMUNE SYSTEM/DE NOVO PROTEIN / Immunogen / Malaria / DE NOVO PROTEIN / IMMUNE SYSTEM-DE NOVO PROTEIN complex
Biological speciesHomo sapiens (human)
Plasmodium falciparum (malaria parasite P. falciparum)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.6 Å
AuthorsGarfinkle, S.E. / Lin, Z.J. / Pallesen, J.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Proc Natl Acad Sci U S A / Year: 2025
Title: Machine learning enables de novo multiepitope design of circumsporozoite protein to target trimeric L9 antibody.
Authors: J Andrew D Nelson / Samuel E Garfinkle / Zi Jie Lin / Joyce Park / Amber J Kim / Kelly Bayruns / Madison E McCanna / Kylie M Konrath / Colby J Agostino / Daniel W Kulp / Audrey R Odom John / Jesper Pallesen /
Abstract: Currently approved vaccines for the prevention of malaria provide only partial protection against disease due to high variability in the quality of induced antibodies. These vaccines present the ...Currently approved vaccines for the prevention of malaria provide only partial protection against disease due to high variability in the quality of induced antibodies. These vaccines present the unstructured central repeat region, as well as the C-terminal domain, of the circumsporozoite protein (CSP) of the malaria parasite, [K. L. Williams ., ,1-13 (2024)]. A recently discovered protective monoclonal antibody, L9, recognizes three structured copies of the CSP minor repeat. Similarly to other highly potent antimalarial antibodies, L9 relies on critical homotypic interactions between antibodies for its high protective efficacy [P. Tripathi , , 480-491.e4 (2023); G. M. Martin , ,2815 (2023)]. Here, we report the design of antigens scaffolding one copy of CSP's minor repeat capable of binding L9. To design antigens capable of presenting multiple, structure-based epitopes in one scaffold, we developed a machine learning- driven structural antigen design pipeline, MESODID, tailored to focus on multiepitope vaccine targets. We use this pipeline to design multiple scaffolds that present three copies of the CSP minor repeat. A 3.6 Å cryo-EM structure of our top design, minor repeat targeting immunogen (M-TIM), demonstrates that M-TIM successfully orients three copies of L9, effectively recapitulating its critical homotypic interactions. The wide prevalence of repeated epitopes in key vaccine targets, such as HIV-1 Envelope, SARS-CoV-2 spike, and Influenza Hemagglutinin, suggests that MESODID will have broad utility in creating antigens that incorporate such epitopes, offering a powerful approach to developing vaccines against a range of challenging infections, including malaria.
History
DepositionFeb 5, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 10, 2025Provider: repository / Type: Initial release
Revision 1.0Dec 10, 2025Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Dec 10, 2025Data content type: Additional map / Part number: 1 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0Dec 10, 2025Data content type: Additional map / Part number: 2 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0Dec 10, 2025Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0Dec 10, 2025Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Dec 10, 2025Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Dec 10, 2025Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Dec 10, 2025Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.1Dec 17, 2025Group: 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.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.identifier_ORCID / _citation_author.name / _em_admin.last_update
Revision 1.1Dec 17, 2025Data content type: EM metadata / Data content type: EM metadata / EM metadata / Group: Database references / Experimental summary / Data content type: EM metadata / EM metadata / EM metadata / Category: citation / citation_author / em_admin
Data content type: EM metadata / EM metadata ...EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.identifier_ORCID / _citation_author.name / _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: L9 Fab heavy chain
B: L9 Fab light chain
C: L9 Fab heavy chain
D: L9 Fab light chain
H: L9 Fab heavy chain
I: L9-targeting immunogen
L: L9 Fab light chain


Theoretical massNumber of molelcules
Total (without water)164,8297
Polymers164,8297
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

#1: Antibody L9 Fab heavy chain


Mass: 24475.436 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293 / Production host: Homo sapiens (human)
#2: Antibody L9 Fab light chain


Mass: 23597.254 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293 / Production host: Homo sapiens (human)
#3: Protein L9-targeting immunogen


Mass: 20610.611 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: The majority of the backbone and sequence was designed de-novo, but small fragments of the P. falciparum protein CSP are included.
Source: (gene. exp.) Plasmodium falciparum (malaria parasite P. falciparum)
Plasmid: pVax / Cell line (production host): HEK293 / Production host: Homo sapiens (human)
Has protein modificationY
Source detailsThe L9-targeting immunogen contains small fragments of the P. falciparum protein CSP that bind to ...The L9-targeting immunogen contains small fragments of the P. falciparum protein CSP that bind to antibody L9, though the majority of the backbone and sequence are de-novo.

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: De novo immunogen bound to three copies of L9 Fab / Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES
Molecular weightValue: 0.17 MDa / Experimental value: YES
Buffer solutionpH: 7
SpecimenConc.: 0.03 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Details: Graphene oxide grids, particles concentrated near graphene oxide
Specimen supportGrid material: GOLD
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / 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: 2500 nm / Nominal defocus min: 1500 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k)

-
Processing

EM software
IDNameVersionCategory
1RELION5.0.0particle selection
2cryoSPARC4.3.1particle selection
3EPUimage acquisition
5cryoSPARC4.3.1CTF correction
10cryoSPARC4.3.1initial Euler assignment
11cryoSPARC4.3.1final Euler assignment
13cryoSPARC4.3.13D reconstruction
14PHENIX1.21.1model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 5667474
3D reconstructionResolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 434079 / Symmetry type: POINT

+
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