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We recently found that TPT is a particularly strong agonist of PPAR\u03b3. To elucidate the mechanism underlying organotin-dependent PPAR\u03b3 activation, we here analyzed the interactions of PPAR\u03b3 ligand-binding domain (LBD) with TPT and TBT by using X-ray crystallography and mass spectroscopy in conjunction with cell-based activity assays. Crystal structures of PPAR\u03b3-LBD\/TBT and PPAR\u03b3-LBD\/TPT complexes were determined at 1.95 \u00c5 and 1.89 \u00c5, respectively. Specific binding of organotins is achieved through non-covalent ionic interactions between the sulfur atom of Cys285 and the tin atom. Comparisons of the determined structures suggest that the strong activity of TPT arises through interactions with helix 12 of LBD primarily via \u03c0-\u03c0 interactions. Our findings elucidate the structural basis of PPAR\u03b3 activation by TPT.<\/jats:p>","DOI":"10.1038\/srep08520","type":"journal-article","created":{"date-parts":[[2015,2,17]],"date-time":"2015-02-17T10:20:02Z","timestamp":1424168402000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Structural basis for PPAR\u03b3 transactivation by endocrine-disrupting organotin compounds"],"prefix":"10.1038","volume":"5","author":[{"given":"Shusaku","family":"Harada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youhei","family":"Hiromori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Kawahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Fukakusa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Maruno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Noda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susumu","family":"Uchiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiichi","family":"Fukui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-ichi","family":"Nishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisamitsu","family":"Nagase","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadayasu","family":"Ohkubo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Nakanishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,2,17]]},"reference":[{"key":"BFsrep08520_CR1","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1038\/358771a0","volume":"358","author":"SA Kliewer","year":"1992","unstructured":"Kliewer, S. 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