Journal
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume 23, Issue 7, Pages 656-662Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.3245
Keywords
-
Funding
- National Institute of Allergy and Infectious Diseases (NIAID) [R01AI091823, R21AI123920, R01AI096169]
- National Institute of Neurological Disorders and Stroke (NINDS) [R01NS080833]
- Bundesministerium fur Bildung and Forschung [FK031A212A, FK031A212B]
- National Institute of General Medical Sciences [P41 GM103403]
- NIH-ORIP HEI [S10 RR029205]
- US Department of Energy (DOE) Office of Science by Argonne National Laboratory - US DOE [DE-AC02-06CH11357]
Ask authors/readers for more resources
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-angstrom-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available