Title : N-linked glycosylation of
SV2 is required for binding and uptake of botulinum
neurotoxin A A. Botulinum
neurotoxin serotype A1 (BoNT/A1), a licensed drug widely used for medical and cosmetic applications, exerts its action by invading motoneurons
Abstract :
- Here we report a 2.0-Å-resolution crystal structure of the BoNT/A1 receptor-binding domain in complex with its neuronal receptor , glycosylated human SV2C
- We found that the neuronal tropism of BoNT/A1 requires recognition of both the peptide moiety and an N-linked glycan on SV2
- This N-glycan-which is conserved in all SV2 isoforms across vertebrates-is essential for BoNT/A1 binding to neurons and for its potent neurotoxicity
- The glycan-binding interface on SV2 is targeted by a human BoNT/A1-neutralizing antibody currently licensed as an antibotulism drug
- Our studies reveal a new paradigm of host-pathogen interactions, in which pathogens exploit conserved host post-translational modifications, thereby achieving highly specific receptor binding while also tolerating genetic changes across multiple isoforms of receptors
Output (sent_index, trigger,
protein,
sugar,
site):
- 0. glycosylation, , SV2, -, -
- 0. glycosylation, , neurotoxin A, -, -
- 1. glycosylated, , SV2C, -, -
- 1. glycosylated, , receptor, -, -
- 4. interface, , SV2, interface, -
Output(Part-Of) (sent_index,
protein,
site):
- 1. A1, domain
- 1. receptor, domain
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):