6ES1

Crystal structure of the binding domain from botulinum neurotoxin A2 bound to extracellular domain of human receptor SV2C

6ES1 の概要

• エントリーDOI: 10.2210/pdb6es1/pdb
• 分子名称: Botulinum neurotoxin type A, Synaptic vesicle glycoprotein 2C, ACETATE ION, ... (4 entities in total)
• 機能のキーワード: receptor, human, clostridium botulinum, binding domain, sv2c, protein binding
• 由来する生物種: Clostridium botulinum; 詳細
• 細胞内の位置: Botulinum neurotoxin A light chain: Secreted. Botulinum neurotoxin A heavy chain: Secreted: Q45894; Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane ; Multi- pass membrane protein : Q496J9
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 65580.88

構造登録者

Gustafsson, R.,Masuyer, G.,Stenmark, P. (登録日: 2017-10-19, 公開日: 2018-04-25, 最終更新日: 2024-01-17)

主引用文献

Gustafsson, R.,Zhang, S.,Masuyer, G.,Dong, M.,Stenmark, P.
Crystal Structure of Botulinum Neurotoxin A2 in Complex with the Human Protein Receptor SV2C Reveals Plasticity in Receptor Binding.
Toxins (Basel), 10:-, 2018

PubMed Abstract: Botulinum neurotoxins (BoNTs) are a family of highly dangerous bacterial toxins, with seven major serotypes (BoNT/A-G). Members of BoNTs, BoNT/A1 and BoNT/B1, have been utilized to treat an increasing number of medical conditions. The clinical trials are ongoing for BoNT/A2, another subtype of BoNT/A, which showed promising therapeutic properties. Both BoNT/A1 and BoNT/A2 utilize three isoforms of synaptic vesicle protein SV2 (SV2A, B, and C) as their protein receptors. We here present a high resolution (2.0 Å) co-crystal structure of the BoNT/A2 receptor-binding domain in complex with the human SV2C luminal domain. The structure is similar to previously reported BoNT/A-SV2C complexes, but a shift of the receptor-binding segment in BoNT/A2 rotates SV2C in two dimensions giving insight into the dynamic behavior of the interaction. Small differences in key residues at the binding interface may influence the binding to different SV2 isoforms, which may contribute to the differences between BoNT/A1 and BoNT/A2 observed in the clinic.

PubMed: 29649119
DOI: 10.3390/toxins10040153

実験手法

X-RAY DIFFRACTION (2 Å)