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Crystal Structure o...
Crystal Structure of Botulinum Neurotoxin A2 in Complex with the Human Protein Receptor SV2C Reveals Plasticity in Receptor Binding
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- Gustafsson, Robert (författare)
- Stockholms universitet,Institutionen för biokemi och biofysik
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Zhang, Sicai (författare)
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- Masuyer, Geoffrey (författare)
- Stockholms universitet,Institutionen för biokemi och biofysik
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Dong, Min (författare)
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- Stenmark, Pål (författare)
- Stockholms universitet,Institutionen för biokemi och biofysik
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(creator_code:org_t)
- 2018-04-12
- 2018
- Engelska.
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Ingår i: Toxins. - : MDPI AG. - 2072-6651. ; 10:4
- Relaterad länk:
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https://doi.org/10.3...
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https://www.mdpi.com...
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https://urn.kb.se/re...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- 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 angstrom) 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Mikrobiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Microbiology (hsv//eng)
Nyckelord
- botulinum toxin
- cell surface receptor
- N-linked glycosylation
- neurotoxin
- protein structure
- protein-protein interaction
- extracellular domain
- membrane protein
- structural biology
- X-ray crystallography
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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