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Title: A viral-fusion-peptide-like molecular switch drives membrane insertion of botulinum neurotoxin A1

Abstract

Botulinum neurotoxin (BoNT) delivers its protease domain across the vesicle membrane to enter the neuronal cytosol upon vesicle acidification. This process is mediated by its translocation domain (HN), but the molecular mechanism underlying membrane insertion of HN remains poorly understood. Here, we report two crystal structures of BoNT/A1 HN that reveal a novel molecular switch (termed BoNT-switch) in HN, where buried α-helices transform into surface-exposed hydrophobic β-hairpins triggered by acidic pH. Locking the BoNT-switch by disulfide trapping inhibited the association of HN with anionic liposomes, blocked channel formation by HN, and reduced the neurotoxicity of BoNT/A1 by up to ~180-fold. Single particle counting studies showed that an acidic environment tends to promote BoNT/A1 self-association on liposomes, which is partly regulated by the BoNT-switch. Furthermore, these findings suggest that the BoNT-switch flips out upon exposure to the acidic endosomal pH, which enables membrane insertion of HN that subsequently leads to LC delivery.

Authors:
 [1];  [2];  [3];  [4];  [5];  [3]; ORCiD logo [3];  [2]; ORCiD logo [1]
+ Show Author Affiliations
  1. Univ. of California, Irvine, CA (United States)
  2. Stony Brook Univ., Stony Brook, NY (United States)
  3. Medizinische Hochschule Hannover, Hannover (Germany)
  4. SLAC National Accelerator Lab., Menlo Park, CA (United States); Stanford Univ., Menlo Park, CA (United States)
  5. Cornell Univ., Argonne, IL (United States)
Publication Date:
Research Org.:
SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1490651
Grant/Contract Number:  
AC02-76SF00515
Resource Type:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 9; Journal Issue: 1; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Lam, Kwok-ho, Guo, Zhuojun, Krez, Nadja, Matsui, Tsutomu, Perry, Kay, Weisemann, Jasmin, Rummel, Andreas, Bowen, Mark E., and Jin, Rongsheng. A viral-fusion-peptide-like molecular switch drives membrane insertion of botulinum neurotoxin A1. United States: N. p., 2018. Web. doi:10.1038/s41467-018-07789-4.
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Lam, Kwok-ho, Guo, Zhuojun, Krez, Nadja, Matsui, Tsutomu, Perry, Kay, Weisemann, Jasmin, Rummel, Andreas, Bowen, Mark E., & Jin, Rongsheng. A viral-fusion-peptide-like molecular switch drives membrane insertion of botulinum neurotoxin A1. United States. https://doi.org/10.1038/s41467-018-07789-4
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Lam, Kwok-ho, Guo, Zhuojun, Krez, Nadja, Matsui, Tsutomu, Perry, Kay, Weisemann, Jasmin, Rummel, Andreas, Bowen, Mark E., and Jin, Rongsheng. Tue . "A viral-fusion-peptide-like molecular switch drives membrane insertion of botulinum neurotoxin A1". United States. https://doi.org/10.1038/s41467-018-07789-4. https://www.osti.gov/servlets/purl/1490651.
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@article{osti_1490651,
title = {A viral-fusion-peptide-like molecular switch drives membrane insertion of botulinum neurotoxin A1},
author = {Lam, Kwok-ho and Guo, Zhuojun and Krez, Nadja and Matsui, Tsutomu and Perry, Kay and Weisemann, Jasmin and Rummel, Andreas and Bowen, Mark E. and Jin, Rongsheng},
abstractNote = {Botulinum neurotoxin (BoNT) delivers its protease domain across the vesicle membrane to enter the neuronal cytosol upon vesicle acidification. This process is mediated by its translocation domain (HN), but the molecular mechanism underlying membrane insertion of HN remains poorly understood. Here, we report two crystal structures of BoNT/A1 HN that reveal a novel molecular switch (termed BoNT-switch) in HN, where buried α-helices transform into surface-exposed hydrophobic β-hairpins triggered by acidic pH. Locking the BoNT-switch by disulfide trapping inhibited the association of HN with anionic liposomes, blocked channel formation by HN, and reduced the neurotoxicity of BoNT/A1 by up to ~180-fold. Single particle counting studies showed that an acidic environment tends to promote BoNT/A1 self-association on liposomes, which is partly regulated by the BoNT-switch. Furthermore, these findings suggest that the BoNT-switch flips out upon exposure to the acidic endosomal pH, which enables membrane insertion of HN that subsequently leads to LC delivery.},
doi = {10.1038/s41467-018-07789-4},
journal = {Nature Communications},
number = 1,
volume = 9,
place = {United States},
year = {2018},
month = {12}
}
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Journal Article:
Free Publicly Available Full Text
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https://doi.org/10.1038/s41467-018-07789-4
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Figures / Tables:

Fig. 1 Fig. 1: Biochemical characterization of tHNA. a The structure of BoNT/A1 (PDB code 3BTA). LC, the “belt”, tHN, and HC are colored green, marine, orange, and cyan, respectively. The disulfide linkage between LC and HN is shown as salmon sphere and the BoNT-switch is highlighted in magenta. b, c Cosedimentationmore » of tHNA with liposomes. tHNA was incubated with asolectin liposomes at pH 7.5, 5.0 or 4.4 (b); or incubated with liposomes containing 60/40mol% PC/cholesterol, 30/30/40mol% PC/PS/cholesterol, or 60/40mol% PS/cholesterol at pH 4.4 (c). After liposomes were pelleted, the proteins in input, supernatant, and pellet fractions were analyzed by SDS-PAGE. These experiments were performed in triplicate and quantification of protein band intensities are shown in Supplementary Fig. 11. Uncropped images of gels are shown in Supplementary Fig. 13. d Calcein dye release assay. tHNA was tested with four different liposomes loaded with 50mM calcein at pH 4.6 or pH 7.0, whereas liposomes were composed of DOPC alone, 80/20 mol% DOPC/DOPS, 60/40 mol% DOPC/DOPS, or asolectin. The rate of calcein dye release was determined based on the increase of fluorescence at 525 nm during excitation at 493 nm. Error bars indicate SD of triplicate measurements. e Membrane depolarization assay. Liposomes composed of 70/20/10 mol% DOPC/DOPS/cholesterol were polarized at a positive internal voltage by adding valinomycin in the presence of a transmembrane KCl gradient. Membrane potential was measured using the voltage-sensitive fluorescence dye ANS. After 3 min, tHNA was added at the indicated buffer pH. The data are presented as mean ± S.D., n =3« less
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Works referenced in this record:

Botulinum Neurotoxin Is Shielded by NTNHA in an Interlocked Complex
journal, February 2012

Structure of influenza haemagglutinin at the pH of membrane fusion
journal, September 1994

  • Bullough, Per A.; Hughson, Frederick M.; Skehel, John J.
  • Nature, Vol. 371, Issue 6492
  • DOI: 10.1038/371037a0

Uniqueness of ab initio shape determination in small-angle scattering
journal, April 2003

  • Volkov, Vladimir V.; Svergun, Dmitri I.
  • Journal of Applied Crystallography, Vol. 36, Issue 3, p. 860-864
  • DOI: 10.1107/S0021889803000268

Overview of the CCP 4 suite and current developments
journal, March 2011

  • Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
  • DOI: 10.1107/S0907444910045749

Role of Metals in the Biological Activity of Clostridium botulinum Neurotoxins † , ‡
journal, March 2004

  • Eswaramoorthy, Subramaniam; Kumaran, Desigan; Keller, James
  • Biochemistry, Vol. 43, Issue 8
  • DOI: 10.1021/bi035844k

Formation of ion channels in lipid bilayers by a peptide with the predicted transmembrane sequence of botulinum neurotoxin A
journal, August 1995

  • Oblatt-Montal, Myrta; Yamazaki, Masahito; Nelson, Richard
  • Protein Science, Vol. 4, Issue 8
  • DOI: 10.1002/pro.5560040806

Structure and function of the complete internal fusion loop from Ebolavirus glycoprotein 2
journal, June 2011

  • Gregory, S. M.; Harada, E.; Liang, B.
  • Proceedings of the National Academy of Sciences, Vol. 108, Issue 27
  • DOI: 10.1073/pnas.1104760108

DAMMIF, a program for rapid ab-initio shape determination in small-angle scattering
journal, January 2009

  • Franke, Daniel; Svergun, Dmitri I.
  • Journal of Applied Crystallography, Vol. 42, Issue 2, p. 342-346
  • DOI: 10.1107/S0021889809000338

Diverse binding modes, same goal: The receptor recognition mechanism of botulinum neurotoxin
journal, March 2015

Crucial Role of the Disulfide Bridge between Botulinum Neurotoxin Light and Heavy Chains in Protease Translocation across Membranes
journal, July 2007

  • Fischer, Audrey; Montal, Mauricio
  • Journal of Biological Chemistry, Vol. 282, Issue 40
  • DOI: 10.1074/jbc.M703619200

CRYSOL – a Program to Evaluate X-ray Solution Scattering of Biological Macromolecules from Atomic Coordinates
journal, December 1995

  • Svergun, D.; Barberato, C.; Koch, M. H. J.
  • Journal of Applied Crystallography, Vol. 28, Issue 6
  • DOI: 10.1107/S0021889895007047

Viral membrane fusion
journal, May 2015

Folding of β-sheet membrane proteins: a hydrophobic hexapeptide model
journal, April 1998

  • Wimley, William C.; Hristova, Kalina; Ladokhin, Alexey S.
  • Journal of Molecular Biology, Vol. 277, Issue 5
  • DOI: 10.1006/jmbi.1998.1640

Botulinum Neurotoxin Heavy Chain Belt as an Intramolecular Chaperone for the Light Chain
journal, January 2007

Effect of pH on the interaction of botulinum neurotoxins A, B and E with liposomes
journal, April 1989

  • Montecucco, C.; Schiavo, G.; Dasgupta, B. R.
  • Biochemical Journal, Vol. 259, Issue 1
  • DOI: 10.1042/bj2590047

Identification of a novel botulinum neurotoxin gene cluster in Enterococcus
journal, January 2018

  • Brunt, Jason; Carter, Andrew T.; Stringer, Sandra C.
  • FEBS Letters, Vol. 592, Issue 3
  • DOI: 10.1002/1873-3468.12969

Neutralisation of specific surface carboxylates speeds up translocation of botulinum neurotoxin type B enzymatic domain
journal, October 2013

ATSAS 2.1 – towards automated and web-supported small-angle scattering data analysis
journal, April 2007

  • Petoukhov, Maxim V.; Konarev, Peter V.; Kikhney, Alexey G.
  • Journal of Applied Crystallography, Vol. 40, Issue s1
  • DOI: 10.1107/S0021889807002853

Interactions of diphtheria toxin with lipid vesicles: determinants of ion channel formation
journal, September 1987

  • Shiver, John W.; Donovan, James J.
  • Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 903, Issue 1
  • DOI: 10.1016/0005-2736(87)90154-4

How do tetanus and botulinum toxins bind to neuronal membranes?
journal, August 1986

Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature
journal, January 2017

Inhibition of botulinum neurotoxins interchain disulfide bond reduction prevents the peripheral neuroparalysis of botulism
journal, December 2015

  • Zanetti, Giulia; Azarnia Tehran, Domenico; Pirazzini, Marcon
  • Biochemical Pharmacology, Vol. 98, Issue 3
  • DOI: 10.1016/j.bcp.2015.09.023

Botulinum neurotoxins: genetic, structural and mechanistic insights
journal, June 2014

  • Rossetto, Ornella; Pirazzini, Marco; Montecucco, Cesare
  • Nature Reviews Microbiology, Vol. 12, Issue 8
  • DOI: 10.1038/nrmicro3295

Mechanisms of pathogen entry through the endosomal compartments
journal, June 2006

  • Gruenberg, Jean; van der Goot, F. Gisou
  • Nature Reviews Molecular Cell Biology, Vol. 7, Issue 7
  • DOI: 10.1038/nrm1959

Membrane Interaction of Botulinum Neurotoxin A Translocation (T) Domain: THE BELT REGION IS A REGULATORY LOOP FOR MEMBRANE INTERACTION
journal, August 2008

  • Galloux, Marie; Vitrac, Heidi; Montagner, Caroline
  • Journal of Biological Chemistry, Vol. 283, Issue 41
  • DOI: 10.1074/jbc.M802557200

Pore-forming toxins: ancient, but never really out of fashion
journal, December 2015

  • Peraro, Matteo Dal; van der Goot, F. Gisou
  • Nature Reviews Microbiology, Vol. 14, Issue 2
  • DOI: 10.1038/nrmicro.2015.3

Real-time measurements of vesicle-SNARE recycling in synapses of the central nervous system
journal, February 2000

  • Sankaranarayanan, Sethuraman; Ryan, Timothy A.
  • Nature Cell Biology, Vol. 2, Issue 4
  • DOI: 10.1038/35008615

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

Structural Basis of the pH-Dependent Assembly of a Botulinum Neurotoxin Complex
journal, November 2014

iMOSFLM : a new graphical interface for diffraction-image processing with MOSFLM
journal, March 2011

  • Battye, T. Geoff G.; Kontogiannis, Luke; Johnson, Owen
  • Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
  • DOI: 10.1107/S0907444910048675

POPS: a fast algorithm for solvent accessible surface areas at atomic and residue level
journal, July 2003

Very fast prediction and rationalization of pKa values for protein-ligand complexes
journal, May 2008

  • Bas, Delphine C.; Rogers, David M.; Jensen, Jan H.
  • Proteins: Structure, Function, and Bioinformatics, Vol. 73, Issue 3
  • DOI: 10.1002/prot.22102

Crystal structure of botulinum neurotoxin type A and implications for toxicity
journal, October 1998

  • Lacy, D. Borden; Tepp, William; Cohen, Alona C.
  • Nature Structural Biology, Vol. 5, Issue 10
  • DOI: 10.1038/2338

Comparison of the pH-induced conformational change of different clostridial neurotoxins
journal, June 2004

  • Puhar, A.; Johnson, E. A.; Rossetto, O.
  • Biochemical and Biophysical Research Communications, Vol. 319, Issue 1
  • DOI: 10.1016/j.bbrc.2004.04.140

Molecular Characterization of a Novel Botulinum Neurotoxin Type H Gene
journal, October 2013

  • Dover, Nir; Barash, Jason R.; Hill, Karen K.
  • The Journal of Infectious Diseases, Vol. 209, Issue 2
  • DOI: 10.1093/infdis/jit450

Diphtheria toxin conformational switching at acidic pH
journal, April 2014

  • Leka, Oneda; Vallese, Francesca; Pirazzini, Marco
  • FEBS Journal, Vol. 281, Issue 9
  • DOI: 10.1111/febs.12783

Clostridial pore-forming toxins: Powerful virulence factors
journal, December 2014

Molecular dissection of botulinum neurotoxin reveals interdomain chaperone function
journal, December 2013

Anthrax Toxin: Receptor Binding, Internalization, Pore Formation, and Translocation
journal, June 2007

PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
  • DOI: 10.1107/S0907444909052925

A Novel Strategy for Development of Recombinant Antitoxin Therapeutics Tested in a Mouse Botulism Model
journal, January 2012

On the translocation of botulinum and tetanus neurotoxins across the membrane of acidic intracellular compartments
journal, March 2016

  • Pirazzini, Marco; Tehran, Domenico Azarnia; Leka, Oneda
  • Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1858, Issue 3
  • DOI: 10.1016/j.bbamem.2015.08.014

Subunit counting in membrane-bound proteins
journal, March 2007

  • Ulbrich, Maximilian H.; Isacoff, Ehud Y.
  • Nature Methods, Vol. 4, Issue 4
  • DOI: 10.1038/nmeth1024

Accessory Proteins Stabilize the Acceptor Complex for Synaptobrevin, the 1:1 Syntaxin/SNAP-25 Complex
journal, February 2008

Receptor Binding Enables Botulinum Neurotoxin B to Sense Low pH for Translocation Channel Assembly
journal, September 2011

Medical aspects of toxin weapons
journal, October 2005

Studies of the Mechanistic Details of the pH-dependent Association of Botulinum Neurotoxin with Membranes
journal, June 2011

  • Mushrush, Darren J.; Koteiche, Hanane A.; Sammons, Morgan A.
  • Journal of Biological Chemistry, Vol. 286, Issue 30
  • DOI: 10.1074/jbc.M111.256982

Obstructing Toxin Pathways by Targeted Pore Blockage
journal, September 2012

  • Nestorovich, Ekaterina M.; Bezrukov, Sergey M.
  • Chemical Reviews, Vol. 112, Issue 12
  • DOI: 10.1021/cr300141q

Identification of the synaptic vesicle glycoprotein 2 receptor binding site in botulinum neurotoxin A
journal, February 2014

Botulinum Neurotoxin Devoid of Receptor Binding Domain Translocates Active Protease
journal, December 2008

Atomic structure of anthrax protective antigen pore elucidates toxin translocation
journal, March 2015

  • Jiang, Jiansen; Pentelute, Bradley L.; Collier, R. John
  • Nature, Vol. 521, Issue 7553
  • DOI: 10.1038/nature14247

N-linked glycosylation of SV2 is required for binding and uptake of botulinum neurotoxin A
journal, June 2016

  • Yao, Guorui; Zhang, Sicai; Mahrhold, Stefan
  • Nature Structural & Molecular Biology, Vol. 23, Issue 7
  • DOI: 10.1038/nsmb.3245

Ebolavirus glycoprotein structure and mechanism of entry
journal, November 2009

  • Lee, Jeffrey E.; Saphire, Erica Ollmann
  • Future Virology, Vol. 4, Issue 6
  • DOI: 10.2217/fvl.09.56

Interaction of botulinum and tetanus toxins with the lipid bilayer surface
journal, April 1988

  • Montecucco, C.; Schiavo, G.; Gao, Z.
  • Biochemical Journal, Vol. 251, Issue 2
  • DOI: 10.1042/bj2510379

Free R value: a novel statistical quantity for assessing the accuracy of crystal structures
journal, January 1992

Experimentally determined hydrophobicity scale for proteins at membrane interfaces
journal, October 1996

  • Wimley, William C.; White, Stephen H.
  • Nature Structural & Molecular Biology, Vol. 3, Issue 10
  • DOI: 10.1038/nsb1096-842

Crystal structure of a catalytically active, non-toxic endopeptidase derivative of Clostridium botulinum toxin A
journal, March 2009

  • Masuyer, Geoffrey; Thiyagarajan, Nethaji; James, Peter L.
  • Biochemical and Biophysical Research Communications, Vol. 381, Issue 1
  • DOI: 10.1016/j.bbrc.2009.02.003

Identification of a Botulinum Neurotoxin-like Toxin in a Commensal Strain of Enterococcus faecium
journal, February 2018

Botulinum neurotoxin B recognizes its protein receptor with high affinity and specificity
journal, December 2006

  • Jin, Rongsheng; Rummel, Andreas; Binz, Thomas
  • Nature, Vol. 444, Issue 7122
  • DOI: 10.1038/nature05387

Identification and characterization of a novel botulinum neurotoxin
journal, August 2017

  • Zhang, Sicai; Masuyer, Geoffrey; Zhang, Jie
  • Nature Communications, Vol. 8, Issue 1
  • DOI: 10.1038/ncomms14130

Viral membrane fusion
journal, July 2008

  • Harrison, Stephen C.
  • Nature Structural & Molecular Biology, Vol. 15, Issue 7
  • DOI: 10.1038/nsmb.1456

Exploring the gas access routes in a [NiFeSe] hydrogenase using crystals pressurized with krypton and oxygen
journal, August 2020

  • Zacarias, Sónia; Temporão, Adriana; Carpentier, Philippe
  • JBIC Journal of Biological Inorganic Chemistry, Vol. 25, Issue 6
  • DOI: 10.1007/s00775-020-01814-y

PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome
journal, December 2019

NELL2-Robo3 complex structure reveals mechanisms of receptor activation for axon guidance
journal, March 2020

Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation
journal, February 2021

Overview of the CCP4 suite and current developments.
text, January 2011

  • Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D.
  • Apollo - University of Cambridge Repository
  • DOI: 10.17863/cam.52322

PHENIX: a comprehensive Python-based system for macromolecular structure solution.
text, January 2010

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Apollo - University of Cambridge Repository
  • DOI: 10.17863/cam.45787

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

Formation of ion channels in lipid bilayers by a peptide with the predicted transmembrane sequence of botulinum neurotoxin A
journal, August 1995

  • Oblatt-Montal, Myrta; Yamazaki, Masahito; Nelson, Richard
  • Protein Science, Vol. 4, Issue 8
  • DOI: 10.1002/pro.5560040806

Very fast prediction and rationalization of pKa values for protein-ligand complexes
journal, May 2008

  • Bas, Delphine C.; Rogers, David M.; Jensen, Jan H.
  • Proteins: Structure, Function, and Bioinformatics, Vol. 73, Issue 3
  • DOI: 10.1002/prot.22102

Folding of β-sheet membrane proteins: a hydrophobic hexapeptide model
journal, April 1998

  • Wimley, William C.; Hristova, Kalina; Ladokhin, Alexey S.
  • Journal of Molecular Biology, Vol. 277, Issue 5
  • DOI: 10.1006/jmbi.1998.1640

Interactions of diphtheria toxin with lipid vesicles: determinants of ion channel formation
journal, September 1987

  • Shiver, John W.; Donovan, James J.
  • Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 903, Issue 1
  • DOI: 10.1016/0005-2736(87)90154-4

Structural predictions of the channel-forming region of botulinum neurotoxin heavy chain
journal, April 1995

How do tetanus and botulinum toxins bind to neuronal membranes?
journal, August 1986

Clostridial pore-forming toxins: Powerful virulence factors
journal, December 2014

Comparison of the pH-induced conformational change of different clostridial neurotoxins
journal, June 2004

  • Puhar, A.; Johnson, E. A.; Rossetto, O.
  • Biochemical and Biophysical Research Communications, Vol. 319, Issue 1
  • DOI: 10.1016/j.bbrc.2004.04.140

Crystal structure of a catalytically active, non-toxic endopeptidase derivative of Clostridium botulinum toxin A
journal, March 2009

  • Masuyer, Geoffrey; Thiyagarajan, Nethaji; James, Peter L.
  • Biochemical and Biophysical Research Communications, Vol. 381, Issue 1
  • DOI: 10.1016/j.bbrc.2009.02.003

Receptor Binding Enables Botulinum Neurotoxin B to Sense Low pH for Translocation Channel Assembly
journal, September 2011

Identification of a Botulinum Neurotoxin-like Toxin in a Commensal Strain of Enterococcus faecium
journal, February 2018

Neutralisation of specific surface carboxylates speeds up translocation of botulinum neurotoxin type B enzymatic domain
journal, October 2013

Structural Basis of the pH-Dependent Assembly of a Botulinum Neurotoxin Complex
journal, November 2014

Accessory Proteins Stabilize the Acceptor Complex for Synaptobrevin, the 1:1 Syntaxin/SNAP-25 Complex
journal, February 2008

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

Viral membrane fusion
journal, May 2015

Crystal Structure of the Ebola Virus Membrane Fusion Subunit, GP2, from the Envelope Glycoprotein Ectodomain
journal, November 1998

Obstructing Toxin Pathways by Targeted Pore Blockage
journal, September 2012

  • Nestorovich, Ekaterina M.; Bezrukov, Sergey M.
  • Chemical Reviews, Vol. 112, Issue 12
  • DOI: 10.1021/cr300141q

Crystal structure of botulinum neurotoxin type A and implications for toxicity
journal, October 1998

  • Lacy, D. Borden; Tepp, William; Cohen, Alona C.
  • Nature Structural Biology, Vol. 5, Issue 10
  • DOI: 10.1038/2338

Real-time measurements of vesicle-SNARE recycling in synapses of the central nervous system
journal, February 2000

  • Sankaranarayanan, Sethuraman; Ryan, Timothy A.
  • Nature Cell Biology, Vol. 2, Issue 4
  • DOI: 10.1038/35008615

Free R value: a novel statistical quantity for assessing the accuracy of crystal structures
journal, January 1992

Structure of influenza haemagglutinin at the pH of membrane fusion
journal, September 1994

  • Bullough, Per A.; Hughson, Frederick M.; Skehel, John J.
  • Nature, Vol. 371, Issue 6492
  • DOI: 10.1038/371037a0

Botulinum neurotoxin B recognizes its protein receptor with high affinity and specificity
journal, December 2006

  • Jin, Rongsheng; Rummel, Andreas; Binz, Thomas
  • Nature, Vol. 444, Issue 7122
  • DOI: 10.1038/nature05387

Mechanisms of pathogen entry through the endosomal compartments
journal, June 2006

  • Gruenberg, Jean; van der Goot, F. Gisou
  • Nature Reviews Molecular Cell Biology, Vol. 7, Issue 7
  • DOI: 10.1038/nrm1959

Botulinum neurotoxins: genetic, structural and mechanistic insights
journal, June 2014

  • Rossetto, Ornella; Pirazzini, Marco; Montecucco, Cesare
  • Nature Reviews Microbiology, Vol. 12, Issue 8
  • DOI: 10.1038/nrmicro3295

N-linked glycosylation of SV2 is required for binding and uptake of botulinum neurotoxin A
journal, June 2016

  • Yao, Guorui; Zhang, Sicai; Mahrhold, Stefan
  • Nature Structural & Molecular Biology, Vol. 23, Issue 7
  • DOI: 10.1038/nsmb.3245

Interaction of botulinum and tetanus toxins with the lipid bilayer surface
journal, April 1988

  • Montecucco, C.; Schiavo, G.; Gao, Z.
  • Biochemical Journal, Vol. 251, Issue 2
  • DOI: 10.1042/bj2510379

Effect of pH on the interaction of botulinum neurotoxins A, B and E with liposomes
journal, April 1989

  • Montecucco, C.; Schiavo, G.; Dasgupta, B. R.
  • Biochemical Journal, Vol. 259, Issue 1
  • DOI: 10.1042/bj2590047

Structure and function of the complete internal fusion loop from Ebolavirus glycoprotein 2
journal, June 2011

  • Gregory, S. M.; Harada, E.; Liang, B.
  • Proceedings of the National Academy of Sciences, Vol. 108, Issue 27
  • DOI: 10.1073/pnas.1104760108

Beltless Translocation Domain of Botulinum Neurotoxin A Embodies a Minimum Ion-conductive Channel
journal, December 2011

  • Fischer, Audrey; Sambashivan, Shilpa; Brunger, Axel T.
  • Journal of Biological Chemistry, Vol. 287, Issue 3
  • DOI: 10.1074/jbc.c111.319400

Single Molecule Fluorescence Study of the Bacillus thuringiensis Toxin Cry1Aa Reveals Tetramerization
journal, October 2011

  • Groulx, Nicolas; McGuire, Hugo; Laprade, Raynald
  • Journal of Biological Chemistry, Vol. 286, Issue 49
  • DOI: 10.1074/jbc.m111.296103

Molecular Characterization of a Novel Botulinum Neurotoxin Type H Gene
journal, October 2013

  • Dover, Nir; Barash, Jason R.; Hill, Karen K.
  • The Journal of Infectious Diseases, Vol. 209, Issue 2
  • DOI: 10.1093/infdis/jit450

POPS: a fast algorithm for solvent accessible surface areas at atomic and residue level
journal, July 2003

Phaser crystallographic software
journal, July 2007

  • McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
  • Journal of Applied Crystallography, Vol. 40, Issue 4
  • DOI: 10.1107/s0021889807021206

MolProbity : all-atom structure validation for macromolecular crystallography
journal, December 2009

  • Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1
  • DOI: 10.1107/s0907444909042073

Features and development of Coot
journal, March 2010

  • Emsley, P.; Lohkamp, B.; Scott, W. G.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
  • DOI: 10.1107/s0907444910007493

Diphtheria toxin conformational switching at acidic pH
journal, April 2014

  • Leka, Oneda; Vallese, Francesca; Pirazzini, Marco
  • FEBS Journal, Vol. 281, Issue 9
  • DOI: 10.1111/febs.12783

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journal, December 2008

PHENIX: a comprehensive Python-based system for macromolecular structure solution.
text, January 2010

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Apollo - University of Cambridge Repository
  • DOI: 10.17863/cam.45787

Ebolavirus glycoprotein structure and mechanism of entry
journal, November 2009

  • Lee, Jeffrey E.; Saphire, Erica Ollmann
  • Future Virology, Vol. 4, Issue 6
  • DOI: 10.2217/fvl.09.56

DAMMIF, a program for rapid ab-initio shape determination in small-angle scattering
text, January 2009

Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature
journal, January 2017

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    • Nature Structural & Molecular Biology, Vol. 26, Issue 8
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