5JMC

Receptor binding domain of Botulinum neurotoxin A in complex with rat SV2C

Summary for 5JMC

• Entry DOI: 10.2210/pdb5jmc/pdb
• Related: 5JLV
• Descriptor: Botulinum neurotoxin type A, Synaptic vesicle glycoprotein 2C (3 entities in total)
• Functional Keywords: hydrolase
• Biological source: Clostridium botulinum; More
• Total number of polymer chains: 8
• Total formula weight: 259976.98

Authors

Yao, G.,Zhang, S.,Mahrhold, S.,Lam, K.,Stern, D.,Bagramyan, K.,Perry, K.,Kalkum, M.,Rummel, A.,Dong, M.,Jin, R. (deposition date: 2016-04-28, release date: 2016-06-15, Last modification date: 2023-09-27)

Primary citation

Yao, G.,Zhang, S.,Mahrhold, S.,Lam, K.H.,Stern, D.,Bagramyan, K.,Perry, K.,Kalkum, M.,Rummel, A.,Dong, M.,Jin, R.
N-linked glycosylation of SV2 is required for binding and uptake of botulinum neurotoxin A.
Nat.Struct.Mol.Biol., 23:656-662, 2016

PubMed Abstract: Botulinum neurotoxin serotype A1 (BoNT/A1), a licensed drug widely used for medical and cosmetic applications, exerts its action by invading motoneurons. 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.

PubMed: 27294781
DOI: 10.1038/nsmb.3245

Experimental method

X-RAY DIFFRACTION (2.64 Å)