Evidence map›Paper›PMID 29158482›Full record

ArticleNature communications2017

Structural basis for the unique ganglioside and cell membrane recognition mechanism of botulinum neurotoxin DC.

Sicai Zhang, Ronnie P-A Berntsson, William H Tepp, Liang Tao, Eric A Johnson, Pål Stenmark, Min Dong

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.3field-weighted citation impact, top 7% of its field
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

21 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Frontiers in microbiology · 2022
    Review
  7. Review
  8. Article
  9. Article
  10. Botulinum Neurotoxins: Mechanism of Action.Handbook of experimental pharmacology · 2021
    Review
  11. Article
  12. Article
  13. Article
  14. Gangliosides interact with synaptotagmin to form the high-affinity receptor complex for botulinum neurotoxin B.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  15. Botulinum and Tetanus Neurotoxins.Annual review of biochemistry · 2019
    Review
  16. Article
  17. Review
  18. Review
  19. Review
  20. 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

7 authors at 3 institutions in 2 countries.

Sicai ZhangDepartment of Urology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Ronnie P-A BerntssonDepartment of Biochemistry and Biophysics, Stockholm University, SE-106 91, Stockholm, Sweden.ORCID http://orcid.org/0000-0001-6848-322X
William H TeppDepartment of Bacteriology, University of Wisconsin, Madison, WI, 53706, USA.
Liang TaoDepartment of Urology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Eric A JohnsonDepartment of Bacteriology, University of Wisconsin, Madison, WI, 53706, USA.
Pål StenmarkDepartment of Biochemistry and Biophysics, Stockholm University, SE-106 91, Stockholm, Sweden. Stenmark@dbb.su.se.
Min DongDepartment of Urology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA. min.dong@childrens.harvard.edu.
Boston Children's Hospital · USStockholm University · SEUniversity of Wisconsin–Madison · US

Funding

STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WAYNE I LENCER · 1986 to 2026
$32.4M
SYNAPTIC MECHANISMS IN HIPPOCAMPAL EPILEPTOGENESISP30HD018655 · NICHD · CHILDREN'S HOSPITAL BOSTON · PI POMEROY, SCOTT LOREN · 1985 to 2015
$26.2M
Long-term effects of botulinum neurotoxins on neuronal viabilityR01NS080833 · NINDS · HARVARD MEDICAL SCHOOL · PI Min Dong · 2013 to 2026
$6.8M
Molecular basis of action and pathogenesis of Clostridium difficile toxin BR01AI132387 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI DONG, MIN · 2017 to 2021
$3.5M
NIAID NIH HHS R01 AI132387NICHD NIH HHS P30 HD018655NIDDK NIH HHS P30 DK034854NINDS NIH HHS R01 NS080833
6 · The paper itself

Abstract

Botulinum neurotoxins (BoNTs), the most potent toxins known, are potential bioterrorism agents. It is well established that all seven serotypes of BoNTs (BoNT/A-G) require complex gangliosides as co-receptors. Here, we report that BoNT/DC, a presumed mosaic toxin between BoNT/D and BoNT/C1, binds and enters efficiently into neurons lacking complex gangliosides and shows no reduction in toxicity in mice deficient in complex gangliosides. The co-crystal structure of BoNT/DC with sialyl-Thomsen-Friedenreich antigen (Sialyl-T) suggests that BoNT/DC recognizes only the sialic acid, but not other moieties in gangliosides. Using liposome flotation assays, we demonstrate that an extended loop in BoNT/DC directly interacts with lipid membranes, and the co-occurring sialic acid binding and loop-membrane interactions mediate the recognition of gangliosides in membranes by BoNT/DC. These findings reveal a unique mechanism for cell membrane recognition and demonstrate that BoNT/DC can use a broad range of sialic acid-containing moieties as co-receptors.

Indexed as

AnimalsBinding SitesBotulinum ToxinsBotulismCell MembraneCrystallography, X-RayFemaleGangliosidesHumansMaleMiceN-Acetylneuraminic AcidBotulinum Toxinsbotulinum toxin type Cbotulinum toxin type DGangliosidesN-Acetylneuraminic Acid

Identifiers

PMID29158482
PMCPMC5696347
OpenAlexW2770203146

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.