3aj6

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HA1 (HA33) mutant F179I of botulinum type C progenitor toxin complexed with N-acetylgalactosamine, bound at site II

Structural highlights

3aj6 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 1.48Å
Ligands:NGA
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HA33C_CBCP Agglutinates human erythrocytes (PubMed:2205574). 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 hemagglutinin (HA) component is involved in binding to the upper small intestine through interactions with glycolipids and glycoproteins containing sialic acid moieties (Probable). Binds galactose or oligosaccharides with galactose at their non-reducing end (PubMed:14663070). Binds eukaryotic host mucins; binding is inhibited by N-acetyl-beta-neuraminic acid, N-acetyl-D-galactosamine, galactose, and methyl N-acetyl-beta-neuraminic acid (PubMed:18178224). Binds N-acetyl-beta-neuraminic acid, N-acetyl-D-galactosamine and galactose (but not glucose) via 2 sites (PubMed:18178224, PubMed:21640703).[1] [2] [3] [4] [5] [6]

Publication Abstract from PubMed

A critical role in internalizing the Clostridium botulinum neurotoxin into gastrointestinal cells is played by nontoxic components complexed with the toxin. One of the components, a beta-trefoil lectin has been known as HA33 or HA1. The HA33 from C. botulinum type A (HA33/A) has been predicted to have a single sugar-binding site, while type C HA33 (HA33/C) has two sites. Here we constructed HA33/C mutants and evaluated the binding capacities of the individual sites through mucin-assay and isothermal titration calorimetry. The mutant W176A (site I knockout) had a K(d) value of 31.5mM for galactose (Gal) and 61.3mM for N-acetylgalactosamine (GalNAc), while the K(d) value for N-acetylneuraminic acid (Neu5Ac) was too high to be determined. In contrast, the double mutant N278A/Q279A (site II knockout) had a K(d) value of 11.8mM for Neu5Ac. We also determined the crystal structures of wild-type and the F179I mutant in complex with GalNAc at site II. The results suggest that site I of HA33/C is quite unique in that it mainly recognizes Neu5Ac, and site II seems less important for the lectin specificity. The architectures and the properties of the sugar-binding sites of HA33/C and HA33/A were shown to be drastically different.

Molecular diversity of the two sugar-binding sites of the beta-trefoil lectin HA33/C (HA1) from Clostridium botulinum type C neurotoxin.,Nakamura T, Tonozuka T, Ito S, Takeda Y, Sato R, Matsuo I, Ito Y, Oguma K, Nishikawa A Arch Biochem Biophys. 2011 Aug 1;512(1):69-77. Epub 2011 May 26. PMID:21640703[7]

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

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Citations
6 reviews cite this structure
Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology.
Pirazzini et al. (2017)
5 more
10 other articles
No citations found

See Also

References

  1. ↑ Inoue K, Sobhany M, Transue TR, Oguma K, Pedersen LC, Negishi M. Structural analysis by X-ray crystallography and calorimetry of a haemagglutinin component (HA1) of the progenitor toxin from Clostridium botulinum. Microbiology. 2003 Dec;149(Pt 12):3361-70. PMID:14663070
  2. ↑ Nakamura T, Tonozuka T, Ide A, Yuzawa T, Oguma K, Nishikawa A. Sugar-binding sites of the HA1 subcomponent of Clostridium botulinum type C progenitor toxin. J Mol Biol. 2008 Feb 22;376(3):854-67. Epub 2007 Dec 23. PMID:18178224 doi:10.1016/j.jmb.2007.12.031
  3. ↑ Nakamura T, Tonozuka T, Ito S, Takeda Y, Sato R, Matsuo I, Ito Y, Oguma K, Nishikawa A. Molecular diversity of the two sugar-binding sites of the beta-trefoil lectin HA33/C (HA1) from Clostridium botulinum type C neurotoxin. Arch Biochem Biophys. 2011 Aug 1;512(1):69-77. Epub 2011 May 26. PMID:21640703 doi:10.1016/j.abb.2011.05.012
  4. ↑ Tsuzuki K, Kimura K, Fujii N, Yokosawa N, Indoh T, Murakami T, Oguma K. Cloning and complete nucleotide sequence of the gene for the main component of hemagglutinin produced by Clostridium botulinum type C. Infect Immun. 1990 Oct;58(10):3173-7. PMID:2205574 doi:10.1128/iai.58.10.3173-3177.1990
  5. ↑ 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
  6. ↑ 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
  7. ↑ Nakamura T, Tonozuka T, Ito S, Takeda Y, Sato R, Matsuo I, Ito Y, Oguma K, Nishikawa A. Molecular diversity of the two sugar-binding sites of the beta-trefoil lectin HA33/C (HA1) from Clostridium botulinum type C neurotoxin. Arch Biochem Biophys. 2011 Aug 1;512(1):69-77. Epub 2011 May 26. PMID:21640703 doi:10.1016/j.abb.2011.05.012

Contents


PDB ID 3aj6

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