{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:26:31Z","timestamp":1790832391730,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T00:00:00Z","timestamp":1671408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"GENCI-[CINES]","award":["2017-A0020707206"],"award-info":[{"award-number":["2017-A0020707206"]}]},{"name":"GENCI-[CINES]","award":["2018-A0040707206"],"award-info":[{"award-number":["2018-A0040707206"]}]},{"name":"GENCI-[CINES]","award":["2019-A0060707206"],"award-info":[{"award-number":["2019-A0060707206"]}]},{"name":"GENCI-[CINES]","award":["2020-A0080707206"],"award-info":[{"award-number":["2020-A0080707206"]}]},{"name":"French Association Vaincre la Mucoviscidose","award":["2017-A0020707206"],"award-info":[{"award-number":["2017-A0020707206"]}]},{"name":"French Association Vaincre la Mucoviscidose","award":["2018-A0040707206"],"award-info":[{"award-number":["2018-A0040707206"]}]},{"name":"French Association Vaincre la Mucoviscidose","award":["2019-A0060707206"],"award-info":[{"award-number":["2019-A0060707206"]}]},{"name":"French Association Vaincre la Mucoviscidose","award":["2020-A0080707206"],"award-info":[{"award-number":["2020-A0080707206"]}]},{"name":"Association pour l\u2019Aide \u00e0 la Recherche contre la Mucoviscidose (AARM)","award":["2017-A0020707206"],"award-info":[{"award-number":["2017-A0020707206"]}]},{"name":"Association pour l\u2019Aide \u00e0 la Recherche contre la Mucoviscidose (AARM)","award":["2018-A0040707206"],"award-info":[{"award-number":["2018-A0040707206"]}]},{"name":"Association pour l\u2019Aide \u00e0 la Recherche contre la Mucoviscidose (AARM)","award":["2019-A0060707206"],"award-info":[{"award-number":["2019-A0060707206"]}]},{"name":"Association pour l\u2019Aide \u00e0 la Recherche contre la Mucoviscidose (AARM)","award":["2020-A0080707206"],"award-info":[{"award-number":["2020-A0080707206"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>ABC transporters are large membrane proteins sharing a complex architecture, which comprises two nucleotide-binding domains (NBDs) and two membrane-spanning domains (MSDs). These domains are susceptible to mutations affecting their folding and assembly. In the CFTR (ABCC7) protein, a groove has been highlighted in the MSD1 at the level of the membrane inner leaflet, containing both multiple mutations affecting folding and a binding site for pharmaco-chaperones that stabilize this region. This groove is also present in ABCB proteins, however it is covered by a short elbow helix, while in ABCC proteins it remains unprotected, due to a lower position of the elbow helix in the presence of the ABCC-specific lasso motif. Here, we identified a MSD1 second-site mutation located in the vicinity of the CFTR MSD1 groove that partially rescued the folding defect of cystic fibrosis causing mutations located within MSD1, while having no effect on the most frequent mutation, F508del, located within NBD1. A model of the mutated protein 3D structure suggests additional interaction between MSD1 and MSD2, strengthening the assembly at the level of the MSD intracellular loops. Altogether, these results provide insightful information in understanding key features of the folding and function of the CFTR protein in particular, and more generally, of type IV ABC transporters.<\/jats:p>","DOI":"10.3390\/ijms232416225","type":"journal-article","created":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T01:36:02Z","timestamp":1671500162000},"page":"16225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Acting on the CFTR Membrane-Spanning Domains Interface Rescues Some Misfolded Mutants"],"prefix":"10.3390","volume":"23","author":[{"given":"Nesrine","family":"Baatallah","sequence":"first","affiliation":[{"name":"INSERM, U1151, Institut Necker Enfants Malades (INEM), Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris Cit\u00e9, CNRS, UMR 8253, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5356-2440","authenticated-orcid":false,"given":"Ahmad","family":"Elbahnsi","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Mus\u00e9um National d\u2019Histoire Naturelle, UMR CNRS 7590, Institut de Min\u00e9ralogie, de Physique des Mat\u00e9riaux et de Cosmochimie, IMPMC, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0863-6022","authenticated-orcid":false,"given":"Benoit","family":"Chevalier","sequence":"additional","affiliation":[{"name":"INSERM, U1151, Institut Necker Enfants Malades (INEM), Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris Cit\u00e9, CNRS, UMR 8253, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sol\u00e8ne","family":"Castanier","sequence":"additional","affiliation":[{"name":"INSERM, U1151, Institut Necker Enfants Malades (INEM), Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris Cit\u00e9, CNRS, UMR 8253, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Paul","family":"Mornon","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Mus\u00e9um National d\u2019Histoire Naturelle, UMR CNRS 7590, Institut de Min\u00e9ralogie, de Physique des Mat\u00e9riaux et de Cosmochimie, IMPMC, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwona","family":"Pranke","sequence":"additional","affiliation":[{"name":"INSERM, U1151, Institut Necker Enfants Malades (INEM), Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris Cit\u00e9, CNRS, UMR 8253, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander","family":"Edelman","sequence":"additional","affiliation":[{"name":"INSERM, U1151, Institut Necker Enfants Malades (INEM), Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris Cit\u00e9, CNRS, UMR 8253, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Sermet-Gaudelus","sequence":"additional","affiliation":[{"name":"INSERM, U1151, Institut Necker Enfants Malades (INEM), Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris Cit\u00e9, CNRS, UMR 8253, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Callebaut","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Mus\u00e9um National d\u2019Histoire Naturelle, UMR CNRS 7590, Institut de Min\u00e9ralogie, de Physique des Mat\u00e9riaux et de Cosmochimie, IMPMC, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6920-7761","authenticated-orcid":false,"given":"Alexandre","family":"Hinzpeter","sequence":"additional","affiliation":[{"name":"INSERM, U1151, Institut Necker Enfants Malades (INEM), Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris Cit\u00e9, CNRS, UMR 8253, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3767","DOI":"10.1002\/1873-3468.13935","article-title":"Structural and functional diversity calls for a new classification of ABC transporters","volume":"594","author":"Thomas","year":"2020","journal-title":"FEBS Lett."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1002\/hep.28300","article-title":"A functional classification of ABCB4 variations causing progressive familial intrahepatic cholestasis type 3","volume":"63","author":"Delaunay","year":"2016","journal-title":"Hepatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.mam.2013.05.001","article-title":"Biosynthesis and trafficking of the bile salt export pump, BSEP: Therapeutic implications of BSEP mutations","volume":"37","author":"Soroka","year":"2014","journal-title":"Mol. 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