Crystal structure of botulinum neurotoxin A2 in complex with the human protein receptor SV2C reveals plasticity in receptor binding

Robert Gustafsson, Sicai Zhang, Geoffrey Masuyer, Min Dong, Pål Stenmark

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Botulinum neurotoxins (BoNTs) are a family of highly dangerous bacterial toxins, with seven major serotypes (BoNT/A-G). Members of BoNTs, BoNT/A1 and BoNT/B1, have been utilized to treat an increasing number of medical conditions. The clinical trials are ongoing for BoNT/A2, another subtype of BoNT/A, which showed promising therapeutic properties. Both BoNT/A1 and BoNT/A2 utilize three isoforms of synaptic vesicle protein SV2 (SV2A, B, and C) as their protein receptors. We here present a high resolution (2.0 Å) co-crystal structure of the BoNT/A2 receptor-binding domain in complex with the human SV2C luminal domain. The structure is similar to previously reported BoNT/A-SV2C complexes, but a shift of the receptor-binding segment in BoNT/A2 rotates SV2C in two dimensions giving insight into the dynamic behavior of the interaction. Small differences in key residues at the binding interface may influence the binding to different SV2 isoforms, which may contribute to the differences between BoNT/A1 and BoNT/A2 observed in the clinic.

Original languageEnglish
Article number153
JournalToxins
Volume10
Issue number4
DOIs
Publication statusPublished - 12 Apr 2018

Keywords

  • Botulinum toxin
  • Cell surface receptor
  • Extracellular domain
  • Membrane protein
  • N-linked glycosylation
  • Neurotoxin
  • Protein
  • Protein interaction
  • Protein structure
  • Structural biology
  • X-ray crystallography

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Crystal structure of botulinum neurotoxin A2 in complex with the human protein receptor SV2C reveals plasticity in receptor binding. / Gustafsson, Robert; Zhang, Sicai; Masuyer, Geoffrey; Dong, Min; Stenmark, Pål.

In: Toxins , Vol. 10, No. 4, 153, 12.04.2018.

Research output: Contribution to journalArticle

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