Evidence map›Paper›PMID 40864694›Full record

ArticleScience advances2025

A nut-and-bolt assembly of the bimodular large progenitor botulinum neurotoxin complex.

Kwok-Ho Lam, Linfeng Gao, Adina Przykopanski, Baohua Chen, Ting Huang, Maren Krüger, Anna-Magdalena Bartels, Martin Bernhard Dorner, Kay Perry, Brigitte Gertrud Dorner and 2 more

Abstract read
In one paragraph

Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Kwok-Ho LamDepartment of Physiology and Biophysics, University of California, Irvine, CA 92697, USA.ORCID 0000-0002-7173-6600
Linfeng GaoDepartment of Physiology and Biophysics, University of California, Irvine, CA 92697, USA.ORCID 0000-0001-6194-5145
Adina PrzykopanskiInstitute for Toxicology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
Baohua ChenDepartment of Physiology and Biophysics, University of California, Irvine, CA 92697, USA.ORCID 0000-0002-8859-2762
Ting HuangDepartment of Physiology and Biophysics, University of California, Irvine, CA 92697, USA.
Maren KrügerBiological Toxins, Centre for Biological Threats and Special Pathogens, Robert Koch Institute, Seestrasse 10, 13353 Berlin, Germany.ORCID 0000-0001-9775-3110
Anna-Magdalena BartelsInstitute for Toxicology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
Martin Bernhard DornerBiological Toxins, Centre for Biological Threats and Special Pathogens, Robert Koch Institute, Seestrasse 10, 13353 Berlin, Germany.ORCID 0000-0002-8176-797X
Kay PerryNE-CAT and Department of Chemistry and Chemical Biology, Cornell University, Argonne National Laboratory, Argonne, IL 60439, USA.ORCID 0000-0002-4046-1704
Brigitte Gertrud DornerBiological Toxins, Centre for Biological Threats and Special Pathogens, Robert Koch Institute, Seestrasse 10, 13353 Berlin, Germany.ORCID 0000-0002-5100-2546
Andreas RummelInstitute for Toxicology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.ORCID 0000-0002-0645-1641
Rongsheng JinDepartment of Physiology and Biophysics, University of California, Irvine, CA 92697, USA.ORCID 0000-0003-0348-7363

Funding

User Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI STEVEN E EALICK · 2018 to 2026
$34.2M
Developing broad-spectrum therapeutics against C. difficile toxinsR01AI158503 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI JIN, RONGSHENG · 2021 to 2025
$3.9M
A versatile structure-based therapeutic platform for development of VHH-based antitoxin and antiviral agentsR01AI173059 · NIAID · TUFTS UNIVERSITY BOSTON · PI JIN, RONGSHENG, SHOEMAKER, CHARLES BIX · 2023 to 2025
$3.2M
Molecular mechanisms of botulinum neurotoxin neutralizationR01AI125704 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI JIN, RONGSHENG, SHOEMAKER, CHARLES BIX · 2016 to 2020
$3.0M
Pixel Array Detector for Macromolecular CrystallographyS10OD021527 · OD · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2016 to 2016
$2.0M
Resolving the intoxication mechanism of botulinum neurotoxins using single molecule structural biologyR01GM151334 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI Mark E Bowen · 2023 to 2026
$1.4M
NIAID NIH HHS R01 AI125704NIAID NIH HHS R01 AI158503NIAID NIH HHS R01 AI173059NIGMS NIH HHS P30 GM124165NIGMS NIH HHS R01 GM151334NIH HHS S10 OD021527
6 · The paper itself

Abstract

Botulinum neurotoxin serotype A (BoNT/A) is naturally produced by bacteria along with four nontoxic neurotoxin-associated proteins (NTNH, HA70, HA33, and HA17), forming a bimodular large progenitor toxin complex (L-PTC). The BoNT/A-NTNH complex protects the toxin from adverse environment, while the complex consisting of HA proteins facilitates toxin absorption during oral intoxication. How these two independent modules assemble into the L-PTC remains unclear. Here, we report the crystal structure of the BoNT/A-NTNH-HA70 complex at ~2.9-Å resolution. The structure reveals that the BoNT/A-NTNH complex is anchored into a concentric double β-barrel channel of trimeric HA70 through a short β-hairpin of NTNH (termed nLoop), resembling a nut-and-bolt attachment. We find that the nLoop of NTNH is strictly conserved across HA-containing BoNT complexes and that NTNH-HA70 binding is interchangeable among them. Furthermore, we demonstrate that the nLoop functions as a minimal motif enabling attachment of a protein-of-interest to the HA complex, with potential applications in oral biologics delivery.

Indexed as

Botulinum Toxins, Type ANeurotoxinsAmino Acid SequenceBacterial ProteinsCrystallography, X-RayModels, MolecularProtein BindingProtein ConformationProtein MultimerizationBacterial ProteinsBotulinum Toxins, Type ANeurotoxins

Identifiers

PMID40864694
PMCPMC12383247

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.