[English] 日本語
Yorodumi Papers
- Database of articles cited by EMDB/PDB/SASBDB data -

+
Search query

Keywords
Structure methods
Author
Journal
IF

-
Structure paper

TitleCryo-EM structures of engineered Shiga toxin-based immunogens capable of eliciting neutralizing antibodies with therapeutic potential against hemolytic uremic syndrome.
Journal, issue, pagesProtein Sci, Vol. 34, Issue 6, Page e70178, Year 2025
Publish dateMay 24, 2025
AuthorsAlejandro Ezequiel Cristófalo / Arvind Sharma / María Laura Cerutti / Kedar Sharma / Roberto Melero / Romina Pardo / Fernando Alberto Goldbaum / Mario Borgnia / Vanesa Zylberman / Lisandro Horacio Otero /
PubMed AbstractShiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) is a serious disease that causes renal failure predominantly in children. Despite its significant impact, there ...Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) is a serious disease that causes renal failure predominantly in children. Despite its significant impact, there are currently no licensed vaccines or effective therapies available. The B subunits of Shiga toxins 1 and 2 (Stx1B and Stx2B) are suitable targets for developing neutralizing antibodies, but their pentameric assembly is unstable when isolated from the whole toxin. Taking advantage of the oligomeric symmetry shared between Stx1B and Stx2B with the lumazine synthase from Brucella spp. (BLS), we have previously engineered the chimeric toxoids BLS-Stx1B and BLS-Stx2B as immunogens to generate therapeutic equine polyclonal antibodies. The resulting product (INM004) has successfully passed Phases 1 and 2 clinical trials, and a Phase 3 has been launched in Argentina and seven European countries. In this work, we present the cryo-electron microscopy structures of BLS-Stx1B and BLS-Stx2B, which confirm that these engineered immunogens effectively stabilize the StxB pentamers. Moreover, our results reveal that both chimeric constructs present high flexibility at their extremes, corresponding to motions of the StxBs with respect to the BLS core. Additionally, we present structural evidence of the interaction between the chimeras and polyclonal Fab (pFab) fragments derived from INM004, demonstrating that the elicited neutralizing antibodies block most of the interaction surface of the toxins with their cellular receptors. These findings further validate this promising antibody-based therapy for mitigating STEC-HUS and demonstrate that the BLS-Stx1B and BLS-Stx2B chimeras are potential candidates for developing a human vaccine.
External linksProtein Sci / PubMed:40411437 / PubMed Central
MethodsEM (single particle)
Resolution2.37 - 8.4 Å
Structure data

42072

8uav

EMDB-42072, PDB-8uav:
Cryo-EM Structure of Brucella Abortus Lumazine Synthase (BLS) Engineered with Shiga Toxin I subunit B (Stx1B)
Method: EM (single particle) / Resolution: 2.37 Å

42073

8uaw

EMDB-42073, PDB-8uaw:
Cryo-EM Structure of Brucella Abortus Lumazine Synthase (BLS) Engineered with Shiga Toxin II subunit B (Stx2B)
Method: EM (single particle) / Resolution: 2.97 Å

EMDB-48123: Cryo-EM Map of Brucella Abortus Lumazine Synthase (BLS) Engineered with Shiga Toxin I subunit B (Stx1B) Complexed with Equine Polyclonal Fab Fragments (Complex 1)
Method: EM (single particle) / Resolution: 8.26 Å

EMDB-48124: Cryo-EM Map of Brucella Abortus Lumazine Synthase (BLS) Engineered with Shiga Toxin I subunit B (Stx1B) Complexed with Equine Polyclonal Fab Fragments (Complex 2)
Method: EM (single particle) / Resolution: 8.23 Å

EMDB-48125: Cryo-EM Map of Brucella Abortus Lumazine Synthase (BLS) Engineered with Shiga Toxin I subunit B (Stx1B) Complexed with Equine Polyclonal Fab Fragments (Complex 3)
Method: EM (single particle) / Resolution: 8.31 Å

EMDB-48126: Cryo-EM Map of Brucella Abortus Lumazine Synthase (BLS) Engineered with Shiga Toxin II subunit B (Stx2B) Complexed with Equine Polyclonal Fab Fragments (Complex 1)
Method: EM (single particle) / Resolution: 8.32 Å

EMDB-48127: Cryo-EM Map of Brucella Abortus Lumazine Synthase (BLS) Engineered with Shiga Toxin II subunit B (Stx2B) Complexed with Equine Polyclonal Fab Fragments (Complex 2)
Method: EM (single particle) / Resolution: 8.24 Å

EMDB-48128: Cryo-EM Map of Brucella Abortus Lumazine Synthase (BLS) Engineered with Shiga Toxin II subunit B (Stx2B) Complexed with Equine Polyclonal Fab Fragments (Complex 3)
Method: EM (single particle) / Resolution: 8.25 Å

EMDB-48129: Cryo-EM Map of Brucella Abortus Lumazine Synthase (BLS) Engineered with Shiga Toxin II subunit B (Stx2B) Complexed with Equine Polyclonal Fab Fragments (Complex 4)
Method: EM (single particle) / Resolution: 8.4 Å

EMDB-48130: Cryo-EM Map of Brucella Abortus Lumazine Synthase (BLS) Engineered with Shiga Toxin II subunit B (Stx2B) Complexed with Equine Polyclonal Fab Fragments (Complex 5)
Method: EM (single particle) / Resolution: 8.4 Å

Source
  • escherichia coli o157:h7 (bacteria)
  • Brucella abortus biovar 1 (strain 9-941)
  • brucella abortus bv. 1 str. 9-941 (bacteria)
  • brucella abortus biovar 1 (strain 9-941) (bacteria)
KeywordsTOXIN / CHIMERA / SHIGA / IMMUNOGEN

+
About Yorodumi Papers

-
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 Papers

Database of articles cited by EMDB/PDB/SASBDB data

  • Database of articles cited by EMDB, PDB, and SASBDB entries
  • Using PubMed data

Related info.:EMDB / PDB / SASBDB / Yorodumi / EMN Papers / Changes in new EM Navigator and Yorodumi

Read more