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Here we explore the Q141K ABCG2 mutation using a comparative approach, contrasting it with another disease-causing mutation in an ABC transporter, the deletion of Phe-508 (\u0394F508) in the cystic fibrosis transmembrane conductance regulator (CFTR). We found, much like in \u0394F508 CFTR, that the Q141K mutation leads to instability in the nucleotide-binding domain (NBD), a defect that translates to significantly decreased protein expression. However, unlike the CFTR mutant, the Q141K mutation does not interfere with the nucleotide-binding domain\/intracellular loop interactions. This investigation has also led to the identification of critical residues involved in the protein\u2013protein interactions necessary for the dimerization of ABCG2: Lys-473 (K473) and Phe-142 (F142). Finally, we have demonstrated the utility of using small molecules to correct the Q141K defect in expression and function as a possible therapeutic approach for hyperuricemia and gout.<\/jats:p>","DOI":"10.1073\/pnas.1214530110","type":"journal-article","created":{"date-parts":[[2013,3,15]],"date-time":"2013-03-15T08:31:14Z","timestamp":1363336274000},"page":"5223-5228","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":104,"title":["Gout-causing Q141K mutation in ABCG2 leads to instability of the nucleotide-binding domain and can be corrected with small molecules"],"prefix":"10.1073","volume":"110","author":[{"given":"Owen M.","family":"Woodward","sequence":"first","affiliation":[{"name":"Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepali N.","family":"Tukaye","sequence":"additional","affiliation":[{"name":"Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinming","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Greenwell","sequence":"additional","affiliation":[{"name":"Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leeza M.","family":"Constantoulakis","sequence":"additional","affiliation":[{"name":"Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin S.","family":"Parker","sequence":"additional","affiliation":[{"name":"Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjana","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"K\u00f6ttgen","sequence":"additional","affiliation":[{"name":"Renal Division, University Medical Centre Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Maloney","sequence":"additional","affiliation":[{"name":"Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William B.","family":"Guggino","sequence":"additional","affiliation":[{"name":"Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,3,14]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00360-008-0291-7"},{"key":"e_1_3_3_2_2","first-page":"215","article-title":"Hyperuricemia and gout: New insights into pathogenesis and treatment","volume":"65","author":"Pillinger MH","year":"2007","unstructured":"MH Pillinger, P Rosenthal, AM Abeles, Hyperuricemia and gout: New insights into pathogenesis and treatment. 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