8QFT

X-ray structure of non-toxic non-hemagglutinin (NTNH) protein from botulinum neurotoxin serotype X

Summary for 8QFT

• Entry DOI: 10.2210/pdb8qft/pdb
• Related: 8byp
• Descriptor: non-toxic non-hemagglutinin protein X (1 entity in total)
• Functional Keywords: botulinum neurotoxin, progenitor toxin complex, clostridium botulinum, strain 111, toxin
• Biological source: Clostridium botulinum
• Total number of polymer chains: 1
• Total formula weight: 137394.98

Authors

Skerlova, J.,Masuyer, G.,Stenmark, P. (deposition date: 2023-09-04, release date: 2024-08-14, Last modification date: 2024-08-28)

Primary citation

Martinez-Carranza, M.,Skerlova, J.,Lee, P.G.,Zhang, J.,Krc, A.,Sirohiwal, A.,Burgin, D.,Elliott, M.,Philippe, J.,Donald, S.,Hornby, F.,Henriksson, L.,Masuyer, G.,Kaila, V.R.I.,Beard, M.,Dong, M.,Stenmark, P.
Activity of botulinum neurotoxin X and its structure when shielded by a non-toxic non-hemagglutinin protein.
Commun Chem, 7:179-179, 2024

PubMed Abstract: 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 and the crystal structure of the isolated NTNH protein. 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 very weak ganglioside binding and exposed hydrophobic surfaces.

PubMed: 39138288
DOI: 10.1038/s42004-024-01262-8

Experimental method

X-RAY DIFFRACTION (3.3 Å)