{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T02:43:14Z","timestamp":1761964994792},"reference-count":19,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2018,5,25]],"date-time":"2018-05-25T00:00:00Z","timestamp":1527206400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004794","name":"Centre National de la Recherche Scientifique","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004794","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:p>Biallelic missense mutations in <jats:italic>MARS<\/jats:italic> are responsible for rare but severe cases of pulmonary alveolar proteinosis (PAP) prevalent on the island of La R\u00e9union. <jats:italic>MARS<\/jats:italic> encodes cytosolic methionyl\u2010tRNA synthetase (MetRS), an essential translation factor. The multisystemic effects observed in patients with this form of PAP are consistent with a loss\u2010of\u2010function defect in an ubiquitously expressed enzyme. The pathophysiological mechanisms involved in <jats:italic>MARS<\/jats:italic>\u2010related PAP are currently unknown. In this work, we analyzed the effect of the PAP\u2010related mutations in <jats:italic>MARS<\/jats:italic> on the thermal stability and on the catalytic parameters of the MetRS mutants, relative to wild\u2010type. The effect of these mutations on the structural integrity of the enzyme as a member of the cytosolic multisynthetase complex was also investigated. Our results establish that the PAP\u2010related substitutions in MetRS impact the tRNA<jats:sup>Met<\/jats:sup>\u2010aminoacylation reaction especially at the level of methionine recognition, and suggest a direct link between the loss of activity of the enzyme and the pathological disorders in PAP.<\/jats:p>","DOI":"10.1111\/febs.14510","type":"journal-article","created":{"date-parts":[[2018,5,18]],"date-time":"2018-05-18T14:55:35Z","timestamp":1526655335000},"page":"2654-2661","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Mutations in <i>MARS<\/i> identified in a specific type of pulmonary alveolar proteinosis alter methionyl\u2010tRNA synthetase activity"],"prefix":"10.1111","volume":"285","author":[{"given":"Martine","family":"Comisso","sequence":"first","affiliation":[{"name":"Institute for Integrative Biology of the Cell (I2BC) CEA CNRS Univ. Paris\u2010Sud Universit\u00e9 Paris\u2010Saclay Gif\u2010sur\u2010Yvette France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Hadchouel","sequence":"additional","affiliation":[{"name":"Service de Pneumologie et d'Allergologie P\u00e9diatriques AP\u2010HP H\u00f4pital Universitaire Necker\u2010Enfants Malades Paris France"},{"name":"U955 Equipe 4 INSERM Cr\u00e9teil France"},{"name":"Universit\u00e9 Paris Descartes\u2010Sorbonne Paris Cit\u00e9 France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques","family":"de Blic","sequence":"additional","affiliation":[{"name":"Service de Pneumologie et d'Allergologie P\u00e9diatriques AP\u2010HP H\u00f4pital Universitaire Necker\u2010Enfants Malades Paris France"},{"name":"Universit\u00e9 Paris Descartes\u2010Sorbonne Paris Cit\u00e9 France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Mirande","sequence":"additional","affiliation":[{"name":"Institute for Integrative Biology of the Cell (I2BC) CEA CNRS Univ. Paris\u2010Sud Universit\u00e9 Paris\u2010Saclay Gif\u2010sur\u2010Yvette France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,5,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra023226"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.03.010"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-9-85"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1158"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201100626"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2013-305049"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1247363"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-14-106"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.69.1.617"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.3339"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb988"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00048a012"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.690867"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M809636200"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi015670b"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00340a021"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.0001j.x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/136.6.1722S"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/20.18.4741"}],"container-title":["The FEBS Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Ffebs.14510","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.14510","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/febs.14510","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.14510","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T11:53:12Z","timestamp":1694951592000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1111\/febs.14510"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,25]]},"references-count":19,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2018,7]]}},"alternative-id":["10.1111\/febs.14510"],"URL":"https:\/\/doi.org\/10.1111\/febs.14510","archive":["Portico"],"relation":{},"ISSN":["1742-464X","1742-4658"],"issn-type":[{"value":"1742-464X","type":"print"},{"value":"1742-4658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,25]]},"assertion":[{"value":"2017-11-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}