8c8g | pdb_00008c8g
Cryo-EM structure of BoNT/Wo-NTNH complex
Structural highlights
FunctionBXWO_WEIOS When overexpressed the N-terminus (residues 1-476) cleaves rat synaptobrevin-2/VAMP2 between '89-Trp-|-Trp-90' in vitro. This releases the cytoplasmic domain of VAMP2 from the synaptic vesicle membrane, which would prevent the assembly of the trans-SNARE complex on the membrane and thus prevent vesicle-target membrane fusion and neurotransmitter release (PubMed:27443638).[1] Publication Abstract from PubMedThe botulinum neurotoxin-like toxin from Weissella oryzae (BoNT/Wo) is one of the BoNT-like toxins recently identified outside of the Clostridium genus. We show that, like the canonical BoNTs, BoNT/Wo forms a complex with its non-toxic non-hemagglutinin (NTNH) partner, which in traditional BoNT serotypes protects the toxin from proteases and the acidic environment of the hosts' guts. We here report the cryo-EM structure of the 300 kDa BoNT/Wo-NTNH/Wo complex together with pH stability studies of the complex. The structure reveals molecular details of the toxin's interactions with its protective partner. The overall structural arrangement is similar to other reported BoNT-NTNH complexes, but NTNH/Wo uniquely contains two extra bacterial immunoglobulin-like (Big) domains on the C-terminus. Although the function of these Big domains is unknown, they are structurally most similar to bacterial proteins involved in adhesion to host cells. In addition, the BoNT/Wo protease domain contains an internal disulfide bond not seen in other BoNTs. Mass photometry analysis revealed that the BoNT/Wo-NTNH/Wo complex is stable under acidic conditions and may dissociate at neutral to basic pH. These findings established that BoNT/Wo-NTNH/Wo shares the general fold of canonical BoNT-NTNH complexes. The presence of unique structural features suggests that it may have an alternative mode of activation, translocation and recognition of host cells, raising interesting questions about the activity and the mechanism of action of BoNT/Wo as well as about its target environment, receptors and substrates. The cryo-EM structure of the BoNT/Wo-NTNH complex reveals two immunoglobulin-like domains.,Kosenina S, Skerlova J, Zhang S, Dong M, Stenmark P FEBS J. 2024 Feb;291(4):676-689. doi: 10.1111/febs.16964. Epub 2023 Sep 29. PMID:37746829[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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