8byp

Publication Abstract from PubMed

Botulinum neurotoxins (BoNTs) are the most potent toxins known and are used to treat an increasing number of medical disorders. All BoNTs are naturally co-expressed with a protective partner protein (NTNH) with which they form a 300 kDa complex, to resist acidic and proteolytic attack from the digestive tract. We have previously identified a new botulinum neurotoxin serotype, BoNT/X, that has unique and therapeutically attractive properties. We present the cryo-EM structure of the BoNT/X-NTNH/X complex at 3.1 A resolution. Unexpectedly, the BoNT/X complex is stable and protease resistant at both neutral and acidic pH and disassembles only in alkaline conditions. Using the stabilizing effect of NTNH, we isolated BoNT/X and showed that it has very low potency both in vitro and in vivo . Given the high catalytic activity and translocation efficacy of BoNT/X, low activity of the full toxin is likely due to the receptor-binding domain, which presents weak ganglioside binding and exposed hydrophobic surfaces.

Structure and activity of botulinum neurotoxin X.,Martinez-Carranza M, Skerlova J, Lee PG, Zhang J, Burgin D, Elliott M, Philippe J, Donald S, Hornby F, Henriksson L, Masuyer G, Beard M, Dong M, Stenmark P bioRxiv [Preprint]. 2023 Jan 11:2023.01.11.523524. doi: , 10.1101/2023.01.11.523524. PMID:36712025^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.