4LO3

HA17-HA33-LacNac

Summary for 4LO3

• Entry DOI: 10.2210/pdb4lo3/pdb
• Related: 4LO0 4LO1 4LO2 4LO4 4LO5 4LO6 4LO7 4LO8
• Related PRD ID: PRD_900019
• Descriptor: HA-33, HA-17, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-alpha-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: progenitor toxin complex, botulinum neurotoxin, botulism, neurotoxin associated protein, hemagglutinin, carbohydrate/sugar binding, secreted protein, protein transport
• Biological source: Clostridium botulinum; More
• Total number of polymer chains: 3
• Total formula weight: 85999.21

Authors

Lee, K.,Gu, S.,Jin, L.,Le, T.T.,Cheng, L.W.,Strotmeier, J.,Kruel, A.M.,Yao, G.,Perry, K.,Rummel, A.,Jin, R. (deposition date: 2013-07-12, release date: 2013-10-30, Last modification date: 2024-02-28)

Primary citation

Lee, K.,Gu, S.,Jin, L.,Le, T.T.,Cheng, L.W.,Strotmeier, J.,Kruel, A.M.,Yao, G.,Perry, K.,Rummel, A.,Jin, R.
Structure of a Bimodular Botulinum Neurotoxin Complex Provides Insights into Its Oral Toxicity.
Plos Pathog., 9:e1003690-e1003690, 2013

PubMed Abstract: Botulinum neurotoxins (BoNTs) are produced by Clostridium botulinum and cause the fatal disease botulism, a flaccid paralysis of the muscle. BoNTs are released together with several auxiliary proteins as progenitor toxin complexes (PTCs) to become highly potent oral poisons. Here, we report the structure of a ∼760 kDa 14-subunit large PTC of serotype A (L-PTC/A) and reveal insight into its absorption mechanism. Using a combination of X-ray crystallography, electron microscopy, and functional studies, we found that L-PTC/A consists of two structurally and functionally independent sub-complexes. A hetero-dimeric 290 kDa complex protects BoNT, while a hetero-dodecameric 470 kDa complex facilitates its absorption in the harsh environment of the gastrointestinal tract. BoNT absorption is mediated by nine glycan-binding sites on the dodecameric sub-complex that forms multivalent interactions with carbohydrate receptors on intestinal epithelial cells. We identified monosaccharides that blocked oral BoNT intoxication in mice, which suggests a new strategy for the development of preventive countermeasures for BoNTs based on carbohydrate receptor mimicry.

PubMed: 24130488
DOI: 10.1371/journal.ppat.1003690

Experimental method

X-RAY DIFFRACTION (2.249 Å)