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Recent studies have divided the <jats:italic>Leptospira<\/jats:italic> spp. into three groups based on virulence, including pathogenic, intermediate, and saprophytic species. Pathogenic species express a protein family with leucine\u2010rich repeat (LRR) domains, which are less expressed or absent in nonpathogenic species, highlighting the importance of this protein family in leptospirosis. However, the role of LRR domain proteins in the pathogenesis of leptospirosis is still unknown and requires further investigation. In this study, the 3D structure of LSS_01692 (rLRR38) was obtained using X\u2010ray crystallography at a resolution of 3.2\u2009\u00c5. The results showed that rLRR38 forms a typical horseshoe structure with 11 \u03b1\u2010helices and 11 \u03b2\u2010sheets and an antiparallel dimeric structure. The interactions of rLRR38 with extracellular matrix and cell surface receptors were evaluated using ELISA and single\u2010molecule atomic force microscopy. The results showed that rLRR38 interacted with fibronectin, collagen IV, and Toll\u2010like receptor 2 (TLR2). Incubating HK2 cells with rLRR38 induced two downstream inflammation responses (IL\u20106 and MCP\u20101) in the TLR2 signal transduction pathway. The TLR2\u2013TLR1 complex showed the most significant upregulation effects under rLRR38 treatment. Inhibitors also significantly inhibited nuclear factor \u03baB and mitogen\u2010activated protein kinases signals transduction under rLRR38 stimulation. In conclusion, rLRR38 was determined to be a novel LRR domain protein in 3D structure and demonstrated as a TLR2\u2010binding protein that induces inflammatory responses. These structural and functional studies provide a deeper understanding of the pathogenesis of leptospirosis.<\/jats:p>","DOI":"10.1111\/febs.16874","type":"journal-article","created":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T08:40:26Z","timestamp":1685176826000},"page":"4513-4532","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Crystal structure of <i>Leptospira<\/i> LSS_01692 reveals a dimeric structure and induces inflammatory responses through Toll\u2010like receptor 2\u2010dependent <scp>NF\u2010\u03baB<\/scp> and <scp>MAPK<\/scp> signal transduction pathways"],"prefix":"10.1111","volume":"290","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3527-4151","authenticated-orcid":false,"given":"Shen\u2010Hsing","family":"Hsu","sequence":"first","affiliation":[{"name":"Kidney Research Center Chang Gung Memorial Hospital  Taoyuan Taiwan"},{"name":"Department of Medical Biotechnology and Laboratory Science 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