Domain Organization in Clostridium botulinum Neurotoxin Type E Is Unique: Its Implication in Faster Translocation

Kumaran, D.; Eswaramoorthy, S.; Furey, W.; Navaza, Jorge; Sax, M.; Swaminathan, Subramanyam

doi:10.1016/j.jmb.2008.12.027

Cited by 173 publications

(212 citation statements)

References 45 publications

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“…The LC and HC remain covalently linked through a disulfide bond until they encounter reducing conditions in the neuronal cytosol . Crystal structures have been reported for full-length BoNT/A (PDB: 3BTA), BoNT/B (PDB: 1EPW), and BoNT/E (PDB: 3FFZ) (Kumaran et al 2009;Lacy et al 1998;Swaminathan and Eswaramoorthy 2000). All three structures are similar in that they exhibit a modular architecture comprising three domains.…”

Section: Molecular Architecture Of Bontmentioning

confidence: 99%

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Assembly and Function of the Botulinum Neurotoxin Progenitor Complex

Gu¹,

Jin²

2012

Current Topics in Microbiology and Immunology

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Botulinum neurotoxins (BoNTs) are among the most poisonous substances known to man, but paradoxically, BoNT-containing medicines and cosmetics have been used with great success in the clinic. Accidental BoNT poisoning mainly occurs through oral ingestion of food contaminated with Clostridium botulinum. BoNTs are naturally produced in the form of progenitor toxin complexes, which are high molecular weight (up to ~900 kDa) multi-protein complexes composed of BoNT and several non-toxic neurotoxin-associated proteins (NAPs). NAPs protect the inherently fragile BoNTs against the hostile environment of the gastrointestinal tract and help BoNTs pass through the intestinal epithelial barrier before they are released into the general circulation. These events are essential for ingested BoNTs to gain access to motoneurons, where they inhibit neurotransmitter release and cause muscle paralysis. In this review, we discuss the structural basis for assembly of NAPs and BoNT into the progenitor toxin complexes that protect BoNT and facilitate its delivery into the bloodstream.

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Section: Molecular Architecture Of Bontmentioning

confidence: 99%

“…3e). Interestingly, the equivalent linker in BoNT/E (Leu819-Ser850) has no rigid secondary structure, which could explain the flexible domain organization of BoNT/E revealed by the electron microcopy and crystal structures (Fischer et al 2008;Kumaran et al 2009). …”

Section: A Novel Conformation Of Bont/a In the M-ptcmentioning

confidence: 99%

Assembly and Function of the Botulinum Neurotoxin Progenitor Complex

Gu¹,

Jin²

2012

Current Topics in Microbiology and Immunology

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“…1B). Since W is conserved within the GBPs of BoNT serotypes A, B, E, F, G and tetanus toxin (17,20,(44)(45)(46)(47), we propose that this mutation can be introduced into each HCR serotype to generate a potentially less reactive but more potent vaccine. In addition, since BoNT/C and BoNT/D possess comparable aromatic residues within another ganglioside binding loop within the HCR (48,49), we propose that the respective W and F may be modified to A to reduce potential reactivity and enhance vaccine potency.…”

Section: Discussionmentioning

confidence: 99%

Enhancing the Protective Immune Response against Botulism

et al. 2013

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“…The structure of BoNT/E differs significantly from BoNT/A and BoNT/B, displaying a much more compact domains' arrangement [10] although the arrangement could be flexible [48]. This makes comparison with other BoNT's difficult because, for instance, when the center of mass is set at a given distance from the model membrane peripheral charges will be able to approach the membrane at different closest distances and the resulting interactions will be different owing to the damping effect of ionic strength.…”

Section: Molecular Modelsmentioning

confidence: 94%

Electric dipole reorientation in the interaction of botulinum neurotoxins with neuronal membranes

et al. 2009

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Edited by Maurice MontalKeywords: Botulinum neurotoxin Membrane electrostatics Protein dipole Presynaptic membrane a b s t r a c t Botulinum neurotoxins are highly potent toxins capable of rapid and specific interaction with the presynaptic membrane. We have hypothesised that: (1) these neurotoxins possess an electric dipole with the positive pole on receptor binding domain Hc-C and that (2) on approaching the negatively charged presynaptic membrane, they reorient themselves and hit the membrane surface with Hc-C; this electrostatic effect would contribute efficient binding. Electrostatic calculations confirm these hypotheses and strongly indicate that electrostatics effects can play an important role in the unique presynaptic membrane binding properties of these neurotoxins and generally on the interaction of other plasma membrane protein ligands.

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Domain Organization in Clostridium botulinum Neurotoxin Type E Is Unique: Its Implication in Faster Translocation

Cited by 173 publications

References 45 publications

Assembly and Function of the Botulinum Neurotoxin Progenitor Complex

Assembly and Function of the Botulinum Neurotoxin Progenitor Complex

Enhancing the Protective Immune Response against Botulism

Electric dipole reorientation in the interaction of botulinum neurotoxins with neuronal membranes

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