7UIA

Crystal structure of BoNT/E receptor binding domain in complex with SV2 and VHH

7UIA の概要

• エントリーDOI: 10.2210/pdb7uia/pdb
• 分子名称: VHH-G6, SV2Ac, Neurotoxin type E, ... (8 entities in total)
• 機能のキーワード: toxin-receptor complex, toxin
• 由来する生物種: Vicugna pacos; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 150919.18

構造登録者

Liu, Z.,Jin, R.,Chen, P. (登録日: 2022-03-28, 公開日: 2023-04-05, 最終更新日: 2024-10-16)

主引用文献

Liu, Z.,Lee, P.G.,Krez, N.,Lam, K.H.,Liu, H.,Przykopanski, A.,Chen, P.,Yao, G.,Zhang, S.,Tremblay, J.M.,Perry, K.,Shoemaker, C.B.,Rummel, A.,Dong, M.,Jin, R.
Structural basis for botulinum neurotoxin E recognition of synaptic vesicle protein 2.
Nat Commun, 14:2338-2338, 2023

PubMed Abstract: Botulinum neurotoxin E (BoNT/E) is one of the major causes of human botulism and paradoxically also a promising therapeutic agent. Here we determined the co-crystal structures of the receptor-binding domain of BoNT/E (HE) in complex with its neuronal receptor synaptic vesicle glycoprotein 2A (SV2A) and a nanobody that serves as a ganglioside surrogate. These structures reveal that the protein-protein interactions between HE and SV2 provide the crucial location and specificity information for HE to recognize SV2A and SV2B, but not the closely related SV2C. At the same time, HE exploits a separated sialic acid-binding pocket to mediate recognition of an N-glycan of SV2. Structure-based mutagenesis and functional studies demonstrate that both the protein-protein and protein-glycan associations are essential for SV2A-mediated cell entry of BoNT/E and for its potent neurotoxicity. Our studies establish the structural basis to understand the receptor-specificity of BoNT/E and to engineer BoNT/E variants for new clinical applications.

PubMed: 37095076
DOI: 10.1038/s41467-023-37860-8

実験手法

X-RAY DIFFRACTION (2.59 Å)