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-Structure paper
タイトル | Structure of a bimodular botulinum neurotoxin complex provides insights into its oral toxicity. |
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ジャーナル・号・ページ | PLoS Pathog, Vol. 9, Issue 10, Page e1003690, Year 2013 |
掲載日 | 2013年10月10日 |
![]() | Kwangkook Lee / Shenyan Gu / Lei Jin / Thi Tuc Nghi Le / Luisa W Cheng / Jasmin Strotmeier / Anna Magdalena Kruel / Guorui Yao / Kay Perry / Andreas Rummel / Rongsheng Jin / ![]() |
PubMed 要旨 | 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 ...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. |
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手法 | EM (単粒子) / X線回折 |
解像度 | 2.055 - 30.0 Å |
構造データ | ![]() EMDB-2416: ![]() EMDB-2417: ![]() PDB-4lo0: ![]() PDB-4lo1: ![]() PDB-4lo2: ![]() PDB-4lo3: ![]() PDB-4lo4: ![]() PDB-4lo5: ![]() PDB-4lo6: ![]() PDB-4lo7: ![]() PDB-4lo8: |
化合物 | ![]() ChemComp-HOH: ![]() ChemComp-GAL: ![]() ChemComp-CL: |
由来 |
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![]() | PROTEIN TRANSPORT / progenitor toxin complex / botulinum neurotoxin / botulism / neurotoxin associated protein / hemagglutinin / carbohydrate/sugar binding / secreted protein |