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-Structure paper
タイトル | Structure and activity of botulinum neurotoxin X. |
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ジャーナル・号・ページ | bioRxiv, Year 2023 |
掲載日 | 2023年1月11日 |
著者 | Markel Martínez-Carranza / Jana Škerlová / Pyung-Gang Lee / Jie Zhang / Dave Burgin / Mark Elliott / Jules Philippe / Sarah Donald / Fraser Hornby / Linda Henriksson / Geoffrey Masuyer / Matthew Beard / Min Dong / Pål Stenmark |
PubMed 要旨 | Botulinum neurotoxins (BoNTs) are the most potent toxins known and are used to treat an increasing number of medical disorders. All BoNTs are naturally co-expressed with a protective partner protein ...Botulinum neurotoxins (BoNTs) are the most potent toxins known and are used to treat an increasing number of medical disorders. All BoNTs are naturally co-expressed with a protective partner protein (NTNH) with which they form a 300 kDa complex, to resist acidic and proteolytic attack from the digestive tract. We have previously identified a new botulinum neurotoxin serotype, BoNT/X, that has unique and therapeutically attractive properties. We present the cryo-EM structure of the BoNT/X-NTNH/X complex at 3.1 Å resolution. Unexpectedly, the BoNT/X complex is stable and protease resistant at both neutral and acidic pH and disassembles only in alkaline conditions. Using the stabilizing effect of NTNH, we isolated BoNT/X and showed that it has very low potency both and . Given the high catalytic activity and translocation efficacy of BoNT/X, low activity of the full toxin is likely due to the receptor-binding domain, which presents weak ganglioside binding and exposed hydrophobic surfaces. |
リンク | bioRxiv / PubMed:36712025 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.12 Å |
構造データ | EMDB-16330, PDB-8byp: |
由来 |
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キーワード | TOXIN / Botulinum neurotoxin / botulism |