{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:17:26Z","timestamp":1790752646896,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T00:00:00Z","timestamp":1632441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>ABCA3 is a crucial protein of pulmonary surfactant biosynthesis, associated with recessive pulmonary disorders such as neonatal respiratory distress and interstitial lung disease. Mutations are mostly private, and accurate interpretation of variants is mandatory for genetic counseling and patient care. We used 3D structure information to complete the set of available bioinformatics tools dedicated to medical decision. Using the experimental structure of human ABCA4, we modeled at atomic resolution the human ABCA3 3D structure including transmembrane domains (TMDs), nucleotide-binding domains (NBDs), and regulatory domains (RDs) in an ATP-bound conformation. We focused and mapped known pathogenic missense variants on this model. We pinpointed amino-acids within the NBDs, the RDs and within the interfaces between the NBDs and TMDs intracellular helices (IHs), which are predicted to play key roles in the structure and\/or the function of the ABCA3 transporter. This theoretical study also highlighted the possible impact of ABCA3 variants in the cytosolic part of the protein, such as the well-known p.Glu292Val and p.Arg288Lys variants.<\/jats:p>","DOI":"10.3390\/ijms221910282","type":"journal-article","created":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T20:15:32Z","timestamp":1632514532000},"page":"10282","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Structure-Based Understanding of ABCA3 Variants"],"prefix":"10.3390","volume":"22","author":[{"given":"Marion","family":"Onn\u00e9e","sequence":"first","affiliation":[{"name":"Institut Mondor de Recherche Biom\u00e9dicale, Universit\u00e9 Paris Est Creteil, F-94010 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Fanen","sequence":"additional","affiliation":[{"name":"Institut Mondor de Recherche Biom\u00e9dicale, Universit\u00e9 Paris Est Creteil, F-94010 Cr\u00e9teil, France"},{"name":"AP-HP, D\u00e9partement de Biochimie-Biologie Mol\u00e9culaire, Pharmacologie, G\u00e9n\u00e9tique M\u00e9dicale, H\u00f4pital Henri Mondor, F-94010 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Callebaut","sequence":"additional","affiliation":[{"name":"Institut de Min\u00e9ralogie de Physique des Mat\u00e9riaux et de Cosmochimie (IMPMC), Mus\u00e9um National d\u2019Histoire Naturelle, UMR CNRS 7590, Sorbonne Universit\u00e9, F-75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alix","family":"de Becdeli\u00e8vre","sequence":"additional","affiliation":[{"name":"Institut Mondor de Recherche Biom\u00e9dicale, Universit\u00e9 Paris Est Creteil, F-94010 Cr\u00e9teil, France"},{"name":"AP-HP, D\u00e9partement de Biochimie-Biologie Mol\u00e9culaire, Pharmacologie, G\u00e9n\u00e9tique M\u00e9dicale, H\u00f4pital Henri Mondor, F-94010 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.jconrel.2018.10.012","article-title":"Pulmonary Surfactant and Drug Delivery: Focusing on the Role of Surfactant Proteins","volume":"291","author":"Guagliardo","year":"2018","journal-title":"J. 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