3R4U

Cell entry of botulinum neurotoxin type C is dependent upon interaction with two ganglioside molecules

3R4U の概要

• エントリーDOI: 10.2210/pdb3r4u/pdb
• 関連するPDBエントリー: 3R4S
• 分子名称: Botulinum neurotoxin type C1 (2 entities in total)
• 機能のキーワード: botulinum toxins, gangliosides, hydrolase
• 由来する生物種: Clostridium botulinum
• 細胞内の位置: Botulinum neurotoxin C1 light chain: Secreted. Botulinum neurotoxin C1 heavy chain: Secreted: P18640
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 102820.70

構造登録者

Strotmeier, J.,Gu, S.,Jutzi, S.,Mahrhold, S.,Zhou, J.,Pich, A.,Bigalke, H.,Rummel, A.,Jin, R.,Binz, T. (登録日: 2011-03-17, 公開日: 2011-06-08, 最終更新日: 2024-02-21)

主引用文献

Strotmeier, J.,Gu, S.,Jutzi, S.,Mahrhold, S.,Zhou, J.,Pich, A.,Eichner, T.,Bigalke, H.,Rummel, A.,Jin, R.,Binz, T.
The biological activity of botulinum neurotoxin type C is dependent upon novel types of ganglioside binding sites.
Mol.Microbiol., 81:143-156, 2011

PubMed Abstract: The seven botulinum neurotoxins (BoNT) cause muscle paralysis by selectively cleaving core components of the vesicular fusion machinery. Their extraordinary activity primarily relies on highly specific entry into neurons. Data on BoNT/A, B, E, F and G suggest that entry follows a dual receptor interaction with complex gangliosides via an established ganglioside binding region and a synaptic vesicle protein. Here, we report high resolution crystal structures of the BoNT/C cell binding fragment alone and in complex with sialic acid. The WY-motif characteristic of the established ganglioside binding region was located on an exposed loop. Sialic acid was co-ordinated at a novel position neighbouring the binding pocket for synaptotagmin in BoNT/B and G and the sialic acid binding site in BoNT/D and TeNT respectively. Employing synaptosomes and immobilized gangliosides binding studies with BoNT/C mutants showed that the ganglioside binding WY-loop, the newly identified sialic acid-co-ordinating pocket and the area corresponding to the established ganglioside binding region of other BoNTs are involved in ganglioside interaction. Phrenic nerve hemidiaphragm activity tests employing ganglioside deficient mice furthermore evidenced that the biological activity of BoNT/C depends on ganglioside interaction with at least two binding sites. These data suggest a unique cell binding and entry mechanism for BoNT/C among clostridial neurotoxins.

PubMed: 21542861
DOI: 10.1111/j.1365-2958.2011.07682.x

実験手法

X-RAY DIFFRACTION (2.2 Å)