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Also due to their conservation among bacteria including important human pathogens, Clp proteases have recently attracted considerable attention as antibiotic targets. Here, we functionally reconstituted and characterized the ClpXP protease of <jats:italic>Chlamydia trachomatis<\/jats:italic> (ctClpXP), an obligate intracellular pathogen and the causative agent of widespread sexually transmitted diseases in humans. Our <jats:italic>in vitro<\/jats:italic> data show that ctClpXP is formed by a hetero-tetradecameric proteolytic core, composed of two distinct homologs of ClpP (ctClpP1 and ctClpP2), that associates with the unfoldase ctClpX via ctClpP2 for regulated protein degradation. Antibiotics of the ADEP class interfere with protease functions by both preventing the interaction of ctClpX with ctClpP1P2 and activating the otherwise dormant proteolytic core for unregulated proteolysis. Thus, our results reveal molecular insight into ctClpXP function, validating this protease as an antibacterial target.<\/jats:p>","DOI":"10.1038\/s41598-019-50505-5","type":"journal-article","created":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T10:02:32Z","timestamp":1569924152000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["The functional ClpXP protease of Chlamydia trachomatis requires distinct clpP genes from separate genetic loci"],"prefix":"10.1038","volume":"9","author":[{"given":"Stefan","family":"Pan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imran T.","family":"Malik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhana","family":"Thomy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Henrichfreise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4477-2382","authenticated-orcid":false,"given":"Peter","family":"Sass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,10,1]]},"reference":[{"key":"50505_CR1","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/nrmicro.2015.4","volume":"14","author":"AO Olivares","year":"2016","unstructured":"Olivares, A. 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