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The <jats:italic>ha<\/jats:italic> cluster encodes four non\u2010toxic neurotoxin\u2010associated proteins (NAPs) that assemble with BoNTs to protect and enhance their oral toxicity. However, the structure and function of the <jats:italic>orfX<\/jats:italic>\u2010type NAPs remain largely unknown. Here, we report the crystal structures for OrfX1, OrfX2, and an OrfX1\u2013OrfX3 complex, which are encoded in the <jats:italic>orfX<\/jats:italic> cluster of a BoNT\/E1\u2010producing <jats:italic>Clostridium botulinum<\/jats:italic> 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.<\/jats:p>","DOI":"10.1002\/1873-3468.14576","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T04:36:25Z","timestamp":1674102985000},"page":"524-537","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Crystal structures of <scp>OrfX1<\/scp>, <scp>OrfX2<\/scp> and the <scp>OrfX1<\/scp>\u2013<scp>OrfX3<\/scp> complex from the <scp><i>orfX<\/i><\/scp> gene cluster of botulinum neurotoxin <scp>E1<\/scp>"],"prefix":"10.1002","volume":"597","author":[{"given":"Linfeng","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics University of California, Irvine  CA 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P.","family":"Douillard","sequence":"additional","affiliation":[{"name":"Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine University of Helsinki  Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin B.","family":"Dorner","sequence":"additional","affiliation":[{"name":"Biological Toxins, Centre for Biological Threats and Special Pathogens Robert Koch Institute  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kay","family":"Perry","sequence":"additional","affiliation":[{"name":"NE\u2010CAT and Department of Chemistry and Chemical Biology Argonne National Laboratory, Cornell University IL Argonne USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miia","family":"Lindstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine University of Helsinki  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