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Title: Molecular assembly of Clostridium botulinum progenitor M complex of type E

Abstract

Clostridium botulinum neurotoxin (BoNT) is released as a progenitor complex, in association with a non-toxic-non-hemagglutinin protein (NTNH) and other associated proteins. We have determined the crystal structure of M type Progenitor complex of botulinum neurotoxin E [PTC-E(M)], a heterodimer of BoNT and NTNH. The crystal structure reveals that the complex exists as a tight, interlocked heterodimer of BoNT and NTNH. The crystal structure explains the mechanism of molecular assembly of the complex and reveals several acidic clusters at the interface responsible for association at low acidic pH and disassociation at basic/neutral pH. Furthermore, the similarity of the general architecture between the PTC-E(M) and the previously determined PTC-A(M) strongly suggests that the progenitor M complexes of all botulinum serotypes may have similar molecular arrangement, although the neurotoxins apparently can take very different conformation when they are released from the M complex.

Authors:
 [1];  [1];  [2];  [3];  [1]
+ Show Author Affiliations
  1. Brookhaven National Lab. (BNL), Upton, NY (United States)
  2. Brookhaven National Lab. (BNL), Upton, NY (United States); Stony Brook Univ., Stony Brook, NY (United States)
  3. Institute of Advanced Sciences, Dartmouth, MA (United States)
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org.:
Defense Threat Reduction Agency (DTRA)
OSTI Identifier:
1235881
Report Number(s):
BNL-111719-2016-JA
Journal ID: ISSN 2045-2322; 456140124
Grant/Contract Number:  
SC00112704
Resource Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 5; Journal Issue: 11; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Closttidium Botulinum; crystal structure; NTNH; biophysics; electron microscopy; structural biology; X-ray crystallography

Citation Formats

Eswaramoorthy, Subramaniam, Sun, Jingchuan, Li, Huilin, Singh, Bal Ram, and Swaminathan, Subramanyam. Molecular assembly of Clostridium botulinum progenitor M complex of type E. United States: N. p., 2015. Web. doi:10.1038/srep17795.
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Eswaramoorthy, Subramaniam, Sun, Jingchuan, Li, Huilin, Singh, Bal Ram, & Swaminathan, Subramanyam. Molecular assembly of Clostridium botulinum progenitor M complex of type E. United States. https://doi.org/10.1038/srep17795
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Eswaramoorthy, Subramaniam, Sun, Jingchuan, Li, Huilin, Singh, Bal Ram, and Swaminathan, Subramanyam. Mon . "Molecular assembly of Clostridium botulinum progenitor M complex of type E". United States. https://doi.org/10.1038/srep17795. https://www.osti.gov/servlets/purl/1235881.
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@article{osti_1235881,
title = {Molecular assembly of Clostridium botulinum progenitor M complex of type E},
author = {Eswaramoorthy, Subramaniam and Sun, Jingchuan and Li, Huilin and Singh, Bal Ram and Swaminathan, Subramanyam},
abstractNote = {Clostridium botulinum neurotoxin (BoNT) is released as a progenitor complex, in association with a non-toxic-non-hemagglutinin protein (NTNH) and other associated proteins. We have determined the crystal structure of M type Progenitor complex of botulinum neurotoxin E [PTC-E(M)], a heterodimer of BoNT and NTNH. The crystal structure reveals that the complex exists as a tight, interlocked heterodimer of BoNT and NTNH. The crystal structure explains the mechanism of molecular assembly of the complex and reveals several acidic clusters at the interface responsible for association at low acidic pH and disassociation at basic/neutral pH. Furthermore, the similarity of the general architecture between the PTC-E(M) and the previously determined PTC-A(M) strongly suggests that the progenitor M complexes of all botulinum serotypes may have similar molecular arrangement, although the neurotoxins apparently can take very different conformation when they are released from the M complex.},
doi = {10.1038/srep17795},
journal = {Scientific Reports},
number = 11,
volume = 5,
place = {United States},
year = {Mon Dec 07 00:00:00 EST 2015},
month = {Mon Dec 07 00:00:00 EST 2015}
}
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https://doi.org/10.1038/srep17795
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Works referenced in this record:

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    Works referencing / citing this record:

    Purification and Characterization of Recombinant Botulinum Neurotoxin Serotype FA, Also Known as Serotype H
    journal, May 2018

    Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology
    journal, March 2017

    • Pirazzini, Marco; Rossetto, Ornella; Eleopra, Roberto
    • Pharmacological Reviews, Vol. 69, Issue 2
    • DOI: 10.1124/pr.116.012658

    The structure of the tetanus toxin reveals pH-mediated domain dynamics
    journal, December 2018

    Purification and Characterization of Recombinant Botulinum Neurotoxin Serotype FA, Also Known as Serotype H
    journal, May 2018

    Crystal structures of OrfX2 and P47 from a Botulinum neurotoxin OrfX-type gene cluster
    journal, November 2017

    • Gustafsson, Robert; Berntsson, Ronnie P-A; Martínez-Carranza, Markel
    • FEBS Letters, Vol. 591, Issue 22
    • DOI: 10.1002/1873-3468.12889

    The structure of the tetanus toxin reveals pH ‐mediated domain dynamics
    journal, June 2017

    Re: Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology
    journal, January 2019

    Two Feet on the Membrane: Uptake of Clostridial Neurotoxins
    book, January 2016

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