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Central to the capacity of <jats:italic>T.\u00a0pallidum<\/jats:italic> to establish infection is the ability of the pathogen to attach to a diversity of host cells. Many pathogenic bacteria employ leucine-rich repeat (LRR) domain-containing proteins to mediate protein\u2013protein interactions, including attachment to host components and establishment of infection. Intriguingly, <jats:italic>T. pallidum<\/jats:italic> expresses only one putative LRR domain-containing protein (Tp0225) with an unknown function. In an effort to ascribe a function to Tp0225, a comprehensive phylogenetic analysis was first performed; this investigation revealed that Tp0225 clusters with the pathogenic clade of treponemes. Its crystal structure was then determined to 2.0\u2005\u00c5 resolution using Pt SAD phasing, which revealed a noncanonical architecture containing a hexameric LRR core with a discontinuous \u03b2-sheet bridged by solvent molecules. Furthermore, a surface-exposed, hydrophobic pocket, which was found in Tp0225 but is largely absent in canonical LRR domains from other pathogenic bacteria, may serve to coordinate a hydrophobic ligand. Overall, this study provides the first structural characterization of the sole LRR domain-containing protein from <jats:italic>T. pallidum<\/jats:italic> and offers insight into the unique molecular landscape of this important human pathogen.<\/jats:p>","DOI":"10.1107\/s2053230x19007726","type":"journal-article","created":{"date-parts":[[2019,6,26]],"date-time":"2019-06-26T13:05:17Z","timestamp":1561554317000},"page":"489-495","update-policy":"https:\/\/doi.org\/10.1107\/cm_01","source":"Crossref","is-referenced-by-count":6,"title":["Structural characterization of <i>Treponema pallidum<\/i> Tp0225 reveals an unexpected leucine-rich repeat architecture"],"prefix":"10.1107","volume":"75","author":[{"given":"Raghavendran","family":"Ramaswamy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Houston","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca","family":"Loveless","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline E.","family":"Cameron","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin J.","family":"Boulanger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"329","published-online":{"date-parts":[[2019,6,26]]},"reference":[{"key":"us5118_bb1","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1107\/S0907444912001308","volume":"68","author":"Afonine","year":"2012","journal-title":"Acta Cryst. 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