3OBT

Crystal structure of Botulinum neurotoxin serotype D ligand binding domain in complex with N-Acetylneuraminic acid

3OBT の概要

• エントリーDOI: 10.2210/pdb3obt/pdb
• 関連するPDBエントリー: 3OBR
• 分子名称: Botulinum neurotoxin type D, N-acetyl-beta-neuraminic acid, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: neurotoxin, gangalioside, hydrolase
• 由来する生物種: Clostridium botulinum
• 細胞内の位置: Botulinum neurotoxin D light chain: Secreted. Botulinum neurotoxin D heavy chain: Secreted: P19321
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 51642.96

構造登録者

Lee, K.K.,Zong, Y.,Jin, R. (登録日: 2010-08-09, 公開日: 2010-09-08, 最終更新日: 2024-10-30)

主引用文献

Strotmeier, J.,Lee, K.,Volker, A.K.,Mahrhold, S.,Zong, Y.,Zeiser, J.,Zhou, J.,Pich, A.,Bigalke, H.,Binz, T.,Rummel, A.,Jin, R.
Botulinum neurotoxin serotype D attacks neurons via two carbohydrate-binding sites in a ganglioside-dependent manner.
Biochem.J., 431:207-216, 2010

PubMed Abstract: The extraordinarily high toxicity of botulinum neurotoxins primarily results from their specific binding and uptake into neurons. At motor neurons, the seven BoNT (botulinum neurotoxin) serotypes A-G inhibit acetylcholine release leading to flaccid paralysis. Uptake of BoNT/A, B, E, F and G requires a dual interaction with gangliosides and the synaptic vesicle proteins synaptotagmin or SV2 (synaptic vesicle glycoprotein 2), whereas little is known about the cell entry mechanisms of the serotypes C and D, which display the lowest amino acid sequence identity compared with the other five serotypes. In the present study we demonstrate that the neurotoxicity of BoNT/D depends on the presence of gangliosides by employing phrenic nerve hemidiaphragm preparations derived from mice expressing the gangliosides GM3, GM2, GM1 and GD1a, or only GM3 [a description of our use of ganglioside nomenclature is given in Svennerholm (1994) Prog. Brain Res. 101, XI-XIV]. High-resolution crystal structures of the 50 kDa cell-binding domain of BoNT/D alone and in complex with sialic acid, as well as biological analyses of single-site BoNT/D mutants identified two carbohydrate-binding sites. One site is located at a position previously identified in BoNT/A, B, E, F and G, but is lacking the conserved SXWY motif. The other site, co-ordinating one molecule of sialic acid, resembles the second ganglioside-binding pocket (the sialic-acid-binding site) of TeNT (tetanus neurotoxin).

PubMed: 20704566
DOI: 10.1042/BJ20101042

実験手法

X-RAY DIFFRACTION (2 Å)