Stenmark, P., Dupuy, J., Imamura, A., Kiso, M. Amyloid fibrils of the HET-s(218–289) prion form a β solenoid with a triangular hydrophobic core. Correlation of structural elements and infectivity of the HET-s prion. Natural β-sheet proteins use negative design to avoid edge-to-edge aggregation.
Structure-based prediction reveals capping motifs that inhibit β-helix aggregation.
Structural insights into a yeast prion illuminate nucleation and strain diversity. Pentapeptide-repeat proteins that act as topoisomerase poison resistance factors have a common dimer interface. A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA. The Protein Data Bank: a computer-based archival file for macromolecular structures. SV2 is the protein receptor for botulinum neurotoxin A. Identification of fibroblast growth factor receptor 3 (FGFR3) as a protein receptor for botulinum neurotoxin serotype A (BoNT/A). Botulinum neurotoxin: a marvel of protein design. Mechanism of action of tetanus and botulinum neurotoxins. Botulinum A exotoxin in cosmetic dermatology. Botulinum toxin as a biological weapon: medical and public health management. Our findings provide a strong platform for the development of novel antitoxin agents and for the rational design of BoNT/A variants with improved therapeutic properties.Īrnon, S. Competition experiments identified a peptide that inhibits the formation of the complex. SV2C-LD consists of a right-handed, quadrilateral β-helix that associates with BoNT/A-RBD mainly through backbone-to-backbone interactions at open β-strand edges, in a manner that resembles the inter-strand interactions in amyloid structures. Here we determined the high-resolution crystal structure of the BoNT/A receptor-binding domain (BoNT/A-RBD) in complex with the SV2C luminal domain (SV2C-LD). In SV2 proteins, the BoNT/A-binding site has been mapped to the luminal domain 7, but the molecular details of the interaction between BoNT/A and SV2 are unknown. Recently, fibroblast growth factor receptor 3 (FGFR3) has also been reported to be a potential BoNT/A receptor 6. Two types of BoNT/A receptor have been identified, both of which are required for BoNT/A toxicity and are therefore likely to cooperate with each other 5: gangliosides and members of the synaptic vesicle glycoprotein 2 (SV2) family, which are putative transporter proteins that are predicted to have 12 transmembrane domains, associate with the receptor-binding domain of the toxin 5.
BoNT/A application causes long-lasting flaccid paralysis of muscles through inhibiting the release of the neurotransmitter acetylcholine by cleaving synaptosomal-associated protein 25 (SNAP-25) within presynaptic nerve terminals 4. BoNT/A is probably best known for its use as an antiwrinkle agent in cosmetic applications (including Botox and Dysport) 3. Despite this, BoNT/A is used to treat a wide range of common medical conditions such as migraines and a variety of ocular motility and movement disorders 2. Botulinum neurotoxin A (BoNT/A) belongs to the most dangerous class of bioweapons 1.
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