Crystal Structure of the HA3 Subcomponent of Clostridium botulinum Type C Progenitor Toxin

Nakamura, Toshio; Kotani, Mao; Tonozuka, Takashi; Ide, Azusa; Oguma, Keiji; Nishikawa, Atsushi

doi:10.1016/j.jmb.2008.11.039

Cited by 35 publications

(52 citation statements)

References 38 publications

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“…This is consistent with the known spontaneous nicking of native NTNHA in the homologous area, which occurs through an unknown mechanism (Fujita et al 1995;Inoue et al 1996;Miyata et al 2009;Sagane et al 2002). Recombinant forms of HA proteins for various BoNT serotypes have also been produced in several laboratories (Inoue et al 2003;Nakamura et al 2009;Nakamura et al 2008).…”

Section: Naps: the Bodyguards Of Bontssupporting

confidence: 74%

“…The crystal structures of the isolated HAs have been reported for selected serotypes, including HA-17 (BoNT/D), HA-33 (BoNT/A, C, and D), and HA-70 (BoNT/C) (Arndt et al 2005;Hasegawa et al 2007;Inoue et al 2003;Nakamura et al 2009;Nakamura et al 2008). However, it is largely unknown how the HAs assemble with each other and subsequently with BoNT and NTNHA.…”

Section: The Structure Of the Ha Proteinsmentioning

confidence: 99%

“…Domain I of HA-70b is very similar to HA-70a. Domains II and III adopt a similar jelly-roll-like β-sandwich structure (Nakamura et al 2009). Intriguingly, HA-70 forms a three-bladed propeller-like trimer in crystals, with a pore located at the center of the trimer (Fig.…”

Section: The Structure Of the Ha Proteinsmentioning

confidence: 99%

“…5). The pore, estimated to be 33 Å in length and 21 Å in diameter, is a compact cylindrical β-barrel composed of 12 β-strands from HA-70a and the domain I of HA-70b (Nakamura et al 2009). …”

Section: The Structure Of the Ha Proteinsmentioning

confidence: 99%

“…One Nacetylneuraminic acid (Neu5Ac) binding site has been reported in HA-70b of BoNT/C, which is located in a cleft formed by domains II and III (Nakamura et al 2009). The HA-70-Neu5Ac interaction was not well defined in the reported crystal structure, likely due to the low binding affinity of a single Neu5Ac to HA-70.…”

Section: Has Mediate Toxin-host Interactionsmentioning

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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