4en8

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Crystal structure of HA70 (HA3) subcomponent of Clostridium botulinum type C progenitor toxin in complex with alpha 2-6-sialyllactose

Structural highlights

4en8 is a 2 chain structure with sequence from Clostridium botulinum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.6Å
Ligands:BGC, GAL, MRD, PRD_900066, SIA
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HA70C_CBCP The hemagglutinin (HA) component of the progenitor toxin protects the structural integrity of botulinum neurotoxin; may increase internalization of the neurotoxin into the bloodstream of the host (PubMed:9421908). The HA component is involved in binding to the upper small intestine through interactions with glycolipids and glycoproteins containing sialic acid moieties (Probable). Whole protein and the HA-53 chain (but not the HA-22-23 chain) bind to bovine mucin; if the mucin is pretreated with neuraminidase (removes the terminal sialic acid of glycoconjugates) mucin binding is decreased (PubMed:19071137). Has higher affinity for alpha-2,3-sialylated oligosaccharides than alpha-2-6 sialylated oligosaccharides (PubMed:22684008).[1] [2] [3] [4]

Publication Abstract from PubMed

Clostridium botulinum produces the botulinum neurotoxin, forming a large complex as progenitor toxins in association with non-toxic non-hemagglutinin and/or several different hemagglutinin (HA) subcomponents, HA33, HA17 and HA70, which bind to carbohydrate of glycoproteins from epithelial cells in the infection process. To elucidate the carbohydrate recognition mechanism of HA70, X-ray structures of HA70 from type C toxin (HA70/C) in complexes with sialylated oligosaccharides were determined, and a binding assay by the glycoconjugate microarray was performed. These results suggested that HA70/C can recognize both alpha2-3- and alpha2-6-sialylated oligosaccharides, and that it has a higher affinity for alpha2-3-sialylated oligosaccharides.

Carbohydrate recognition mechanism of HA70 from Clostridium botulinum deduced from X-ray structures in complexes with sialylated oligosaccharides.,Yamashita S, Yoshida H, Uchiyama N, Nakakita Y, Nakakita S, Tonozuka T, Oguma K, Nishikawa A, Kamitori S FEBS Lett. 2012 Jul 30;586(16):2404-10. doi: 10.1016/j.febslet.2012.05.055. Epub , 2012 Jun 7. PMID:22684008[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
4 reviews cite this structure
Architecture of the botulinum neurotoxin complex: a molecular machine for protection and delivery.
Lam et al. (2015)
3 more
10 other articles
No citations found

See Also

References

  1. ↑ Nakamura T, Kotani M, Tonozuka T, Ide A, Oguma K, Nishikawa A. Crystal structure of the HA3 subcomponent of Clostridium botulinum type C progenitor toxin. J Mol Biol. 2009 Jan 30;385(4):1193-206. Epub 2008 Nov 27. PMID:19071137 doi:10.1016/j.jmb.2008.11.039
  2. ↑ Yamashita S, Yoshida H, Uchiyama N, Nakakita Y, Nakakita S, Tonozuka T, Oguma K, Nishikawa A, Kamitori S. Carbohydrate recognition mechanism of HA70 from Clostridium botulinum deduced from X-ray structures in complexes with sialylated oligosaccharides. FEBS Lett. 2012 Jul 30;586(16):2404-10. doi: 10.1016/j.febslet.2012.05.055. Epub , 2012 Jun 7. PMID:22684008 doi:10.1016/j.febslet.2012.05.055
  3. ↑ Fujinaga Y, Inoue K, Watanabe S, Yokota K, Hirai Y, Nagamachi E, Oguma K. The haemagglutinin of Clostridium botulinum type C progenitor toxin plays an essential role in binding of toxin to the epithelial cells of guinea pig small intestine, leading to the efficient absorption of the toxin. Microbiology (Reading). 1997 Dec;143 ( Pt 12):3841-3847. doi:, 10.1099/00221287-143-12-3841. PMID:9421908 doi:http://dx.doi.org/10.1099/00221287-143-12-3841
  4. ↑ Fujinaga Y, Inoue K, Watanabe S, Yokota K, Hirai Y, Nagamachi E, Oguma K. The haemagglutinin of Clostridium botulinum type C progenitor toxin plays an essential role in binding of toxin to the epithelial cells of guinea pig small intestine, leading to the efficient absorption of the toxin. Microbiology (Reading). 1997 Dec;143 ( Pt 12):3841-3847. doi:, 10.1099/00221287-143-12-3841. PMID:9421908 doi:http://dx.doi.org/10.1099/00221287-143-12-3841
  5. ↑ Yamashita S, Yoshida H, Uchiyama N, Nakakita Y, Nakakita S, Tonozuka T, Oguma K, Nishikawa A, Kamitori S. Carbohydrate recognition mechanism of HA70 from Clostridium botulinum deduced from X-ray structures in complexes with sialylated oligosaccharides. FEBS Lett. 2012 Jul 30;586(16):2404-10. doi: 10.1016/j.febslet.2012.05.055. Epub , 2012 Jun 7. PMID:22684008 doi:10.1016/j.febslet.2012.05.055

Contents


PDB ID 4en8

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