3FFZ

Domain organization in Clostridium butulinum neurotoxin type E is unique: Its implication in faster translocation

3FFZ の概要

• エントリーDOI: 10.2210/pdb3ffz/pdb
• 分子名称: Botulinum neurotoxin type E, ZINC ION, SODIUM ION, ... (5 entities in total)
• 機能のキーワード: botulinum neurotoxin serotype e, botulism, domain organization, endopeptidase, translocation, hydrolase, membrane, metal-binding, metalloprotease, neurotoxin, protease, secreted, toxin, transmembrane, zinc
• 由来する生物種: Clostridium botulinum
• 細胞内の位置: Botulinum neurotoxin E light chain: Secreted. Botulinum neurotoxin E heavy chain: Secreted: Q00496
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 287910.22

構造登録者

Kumaran, D.,Eswaramoorthy, S.,Swaminathan, S. (登録日: 2008-12-04, 公開日: 2008-12-16, 最終更新日: 2024-10-30)

主引用文献

Kumaran, D.,Eswaramoorthy, S.,Furey, W.,Navaza, J.,Sax, M.,Swaminathan, S.
Domain organization in Clostridium botulinum neurotoxin type E is unique: its implication in faster translocation.
J.Mol.Biol., 386:233-245, 2009

PubMed Abstract: Clostridium botulinum produces seven antigenically distinct neurotoxins [C. botulinum neurotoxins (BoNTs) A-G] sharing a significant sequence homology. Based on sequence and functional similarity, it was believed that their three-dimensional structures will also be similar. Indeed, the crystal structures of BoNTs A and B exhibit similar fold and domain association where the translocation domain is flanked on either side by binding and catalytic domains. Here, we report the crystal structure of BoNT E holotoxin and show that the domain association is different and unique, although the individual domains are similar to those of BoNTs A and B. In BoNT E, both the binding domain and the catalytic domain are on the same side of the translocation domain, and all three have mutual interfaces. This unique association may have an effect on the rate of translocation, with the molecule strategically positioned in the vesicle for quick entry into cytosol. Botulism, the disease caused by BoNT E, sets in faster than any other serotype because of its speedy internalization and translocation, and the present structure offers a credible explanation. We propose that the translocation domain in other BoNTs follows a two-step process to attain translocation-competent conformation as in BoNT E. We also suggest that this translocation-competent conformation in BoNT E is a probable reason for its faster toxic rate compared to BoNT A. However, this needs further experimental elucidation.

PubMed: 19118561
DOI: 10.1016/j.jmb.2008.12.027

実験手法

X-RAY DIFFRACTION (2.65 Å)