7UIB

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

Summary for 7UIB

• Entry DOI: 10.2210/pdb7uib/pdb
• Related: 7UIA
• Descriptor: VHH-G6, SV2, Neurotoxin type E, ... (9 entities in total)
• Functional Keywords: toxin-receptor complex, toxin
• Biological source: Vicugna pacos; More
• Total number of polymer chains: 6
• Total formula weight: 151183.41

Authors

Liu, Z.,Jin, R.,Chen, P. (deposition date: 2022-03-29, release date: 2023-04-05, Last modification date: 2024-10-16)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.77 Å)