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We have previously reported that recombinant flagellins of <jats:italic>T\u00a0pallidum<\/jats:italic> can elicit IL\u20106 and IL\u20108 transcriptions via TLR5 pathway. To identify the domains which induced the pro\u2010inflammatory activity and the importance of the interactions between TLR5 and domains, homology\u2010based modelling and comparative structural analyses revealed that <jats:italic>Tp<\/jats:italic>flagellins can combine with TLR5 directly. Deletion mutations showed that the ND1 domain binding to TLR5 is required but not sufficient in TLR5 activation. Moreover, site\u2010directed mutagenesis analysis indicated that the arginine residue (<jats:italic>Tp<\/jats:italic>flagellins R89) of the ND1 domain and its adjacent residues (<jats:italic>Tp<\/jats:italic>flagellins L93 and E113) constitute a hot spot that elicits IL\u20106, IL\u20108 transcriptions and TLR5 activation, and affects the binding of <jats:italic>Tp<\/jats:italic>flagellins to TLR5. Taken together, these results give insight into the pathogenesis of <jats:italic>T\u00a0pallidum<\/jats:italic> and may contribute to the future design of <jats:italic>Tp<\/jats:italic>flagellins\u2010based therapeutics and syphilis vaccine.<\/jats:p>","DOI":"10.1111\/jcmm.14617","type":"journal-article","created":{"date-parts":[[2019,9,7]],"date-time":"2019-09-07T18:21:59Z","timestamp":1567880519000},"page":"7490-7504","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The N\u2010terminal D1 domain of <i>Treponema pallidum <\/i>flagellin binding to TLR5 is required but not sufficient in activation of TLR5"],"prefix":"10.1111","volume":"23","author":[{"given":"Man","family":"Xu","sequence":"first","affiliation":[{"name":"Institution of Pathogenic Biology, Medical College Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control Hunan Province Cooperative Innovation Center for Molecular Target New 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