Crystal structure of the <scp>OrfX1</scp>–<scp>OrfX3</scp> complex from the <scp>PMP1</scp> neurotoxin gene cluster

Košenina, Sara; Stenmark, Pål

doi:10.1002/1873-3468.14542

Cited by 2 publications

(1 citation statement)

References 41 publications

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“…The function of OrfX proteins is still unknown and it is not clear whether they form a complex with M-PTC. However, all OrfX proteins have been shown to belong to the tubular lipid-binding family of proteins [28][29][30][31].…”

Section: Introductionmentioning

confidence: 99%

The cryo‐EM structure of the BoNT/Wo‐NTNH complex reveals two immunoglobulin‐like domains

Košenina,

Škerlová,

Zhang

et al. 2023

The FEBS Journal

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The 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.

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Section: Introductionmentioning

confidence: 99%

The cryo‐EM structure of the BoNT/Wo‐NTNH complex reveals two immunoglobulin‐like domains

Košenina,

Škerlová,

Zhang

et al. 2023

The FEBS Journal

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View full text Add to dashboard Cite

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Crystal structures of OrfX1, OrfX2 and the OrfX1–OrfX3 complex from the orfX gene cluster of botulinum neurotoxin E1

et al. 2023

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Botulinum neurotoxins (BoNTs) are among the most lethal toxins known to humans, comprising seven established serotypes termed BoNT/A-G encoded in two types of gene clusters (ha and orfX) in BoNT-producing clostridia. The ha cluster encodes four non-toxic neurotoxin-associated proteins (NAPs) that assemble with BoNTs to protect and enhance their oral toxicity. However, the structure and function of the orfX-type NAPs remain largely unknown. Here, we report the crystal structures for OrfX1, OrfX2, and an OrfX1-OrfX3 complex, which are encoded in the orfX cluster of a BoNT/ E1-producing Clostridium botulinum strain associated with human foodborne botulism. These structures lay the foundation for future studies on the potential roles of OrfX proteins in oral intoxication and pathogenesis of BoNTs.

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Crystal structure of the OrfX1–OrfX3 complex from the PMP1 neurotoxin gene cluster

Cited by 2 publications

References 41 publications

The cryo‐EM structure of the BoNT/Wo‐NTNH complex reveals two immunoglobulin‐like domains

The cryo‐EM structure of the BoNT/Wo‐NTNH complex reveals two immunoglobulin‐like domains

Crystal structures of OrfX1, OrfX2 and the OrfX1–OrfX3 complex from the orfX gene cluster of botulinum neurotoxin E1

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