ArticleNature communications2026
A belt-buckle checkpoint regulates the onset of botulinum neurotoxin intoxication.
Baohua Chen, Linfeng Gao, Melvin Bönninger, Ting Huang, Nadja Krez, Weihua Wen, Mark Bowen, Jianlong Lou, James D Marks, Andreas Rummel and 1 more
Abstract read
In one paragraphArticle in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 · Who and what moneyAuthors and funding
11 authors.
Baohua Chen *Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
Linfeng Gao *Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.ORCID 0000-0001-6194-5145 Melvin Bönninger *Institute of Toxicology, Hannover Medical School, Hannover, Germany.
Ting HuangDepartment of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
Weihua WenDepartment of Anesthesia, University of California, San Francisco, Zuckerberg San Francisco General Hospital, San Francisco, CA, USA.
Jianlong LouDepartment of Anesthesia, University of California, San Francisco, Zuckerberg San Francisco General Hospital, San Francisco, CA, USA.
James D MarksDepartment of Anesthesia, University of California, San Francisco, Zuckerberg San Francisco General Hospital, San Francisco, CA, USA.
Andreas RummelInstitute of Toxicology, Hannover Medical School, Hannover, Germany. Rummel.Andreas@mh-hannover.de.ORCID 0000-0002-0645-1641 Rongsheng JinDepartment of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA. r.jin@uci.edu.ORCID 0000-0003-0348-7363 Funding
Development of botulinum neurotoxin immunotherapyU01AI056493 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARKS, JAMES D. · 2003 to 2007
$5.1MA 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
$3.2MMolecular mechanisms of botulinum neurotoxin neutralizationR01AI125704 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI JIN, RONGSHENG, SHOEMAKER, CHARLES BIX · 2016 to 2020
$3.0MResolving 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
$1.4MU.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01AI125704U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01AI173059U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) U01AI056493U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R01GM151334
6 · The paper itselfAbstract
Fast-acting botulinum neurotoxins (BoNTs) are highly desirable for both medical and aesthetic indications, but the underlying mechanism for the differing onset of BoNTs' action remains unknown. Here, we demonstrate that the "belt" of BoNTs, a largely unstructured loop wrapping around their catalytic light chain (LC), is key to onset of intoxication. The more flexible BoNT/E belt promotes quicker LC translocation into the neuronal cytosol, leading to faster onset of action compared to BoNT/A. Furthermore, we discover a "belt-buckle" checkpoint that regulates this process. By loosening the BoNT/A belt-buckle via protein engineering, we enhance its sensitivity to acidic pH, leading to an accelerated onset of action. Conversely, locking the belt-buckle with an antibody neutralizes BoNT/A. Our findings open avenues for developing fast-acting BoNTs and effective countermeasures.
Indexed as
Botulinum ToxinsBotulinum Toxins, Type AAnimalsCytosolHumansHydrogen-Ion ConcentrationNeuronsProtein EngineeringProtein TransportBotulinum ToxinsBotulinum Toxins, Type Abotulinum toxin type E
Identifiers
PMID42337249
PMCPMC13291336
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LicenceCC BY
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