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Here we show that dimerization of AR ligand-binding domain (LBD) is induced by receptor agonists but not by antagonists. The 2.15-\u00c5 crystal structure of homodimeric, agonist- and coactivator peptide-bound AR-LBD unveils a 1,000-\u00c5\n                    <jats:sup>2<\/jats:sup>\n                    large dimerization surface, which harbours over 40 previously unexplained AIS- and PCa-associated point mutations. An AIS mutation in the self-association interface (P767A) disrupts dimer formation\n                    <jats:italic>in vivo<\/jats:italic>\n                    , and has a detrimental effect on the transactivating properties of full-length AR, despite retained hormone-binding capacity. The conservation of essential residues suggests that the unveiled dimerization mechanism might be shared by other nuclear receptors. Our work defines AR-LBD homodimerization as an essential step in the proper functioning of this important transcription factor.\n                  <\/jats:p>","DOI":"10.1038\/ncomms14388","type":"journal-article","created":{"date-parts":[[2017,2,6]],"date-time":"2017-02-06T08:41:45Z","timestamp":1486370505000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":185,"title":["Structure of the homodimeric androgen receptor ligand-binding domain"],"prefix":"10.1038","volume":"8","author":[{"given":"Marta","family":"Nadal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7051-9321","authenticated-orcid":false,"given":"Stefan","family":"Prekovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nerea","family":"Gallastegui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1048-2798","authenticated-orcid":false,"given":"Christine","family":"Helsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montserrat","family":"Abella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Zielinska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Gay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Vilaseca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Taul\u00e8s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan B.","family":"Houtsmuller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin E.","family":"van Royen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8676-7709","authenticated-orcid":false,"given":"Frank","family":"Claessens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Fuentes-Prior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Est\u00e9banez-Perpi\u00f1\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,2,6]]},"reference":[{"key":"BFncomms14388_CR1","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1146\/annurev-physiol-021909-135917","volume":"72","author":"P Huang","year":"2010","unstructured":"Huang, P., Chandra, V. & Rastinejad, F. 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