{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T12:09:21Z","timestamp":1778328561785,"version":"3.51.4"},"reference-count":60,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100006087","name":"Direcci\u00f3n General de Asuntos del Personal Acad\u00e9mico, Universidad Nacional Aut\u00f3noma de M\u00e9xico","doi-asserted-by":"publisher","award":["IA200725"],"award-info":[{"award-number":["IA200725"]}],"id":[{"id":"10.13039\/501100006087","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006087","name":"Direcci\u00f3n General de Asuntos del Personal Acad\u00e9mico, Universidad Nacional Aut\u00f3noma de M\u00e9xico","doi-asserted-by":"publisher","award":["IG200125"],"award-info":[{"award-number":["IG200125"]}],"id":[{"id":"10.13039\/501100006087","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006087","name":"Direcci\u00f3n General de Asuntos del Personal Acad\u00e9mico, Universidad Nacional Aut\u00f3noma de M\u00e9xico","doi-asserted-by":"publisher","award":["IN215122"],"award-info":[{"award-number":["IN215122"]}],"id":[{"id":"10.13039\/501100006087","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011889","name":"Diamond Light Source","doi-asserted-by":"publisher","award":["MX36130\u20103"],"award-info":[{"award-number":["MX36130\u20103"]}],"id":[{"id":"10.13039\/100011889","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006231","name":"Brookhaven National Laboratory","doi-asserted-by":"publisher","award":["306055"],"award-info":[{"award-number":["306055"]}],"id":[{"id":"10.13039\/100006231","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Shwachman\u2010Diamond syndrome (SDS) is a rare genetic disorder characterized by pancreatic insufficiency and neutropenia. While most cases are linked to mutations in the\n                    <jats:italic>SBDS<\/jats:italic>\n                    gene, some involve mutations in the GTPase EFL1. This protein works with SBDS to release the anti\u2010association factor eIF6 from the 60S ribosomal subunit during ribosome biogenesis. The pathogenic EFL1 R1095Q mutant (R1086Q in yeast) exhibits altered guanine nucleotide recognition and impaired eIF6 release, prompting an investigation into its structural consequences. Using the yeast Efl1 orthologue in X\u2010ray hydroxyl radical footprinting experiments, we tracked changes in solvent accessibility caused by the mutation. Although the mutation is situated in domain IV, widespread conformational changes were observed across the protein, particularly in domain I, suggesting a long\u2010range intramolecular communication. Strikingly, the growth defect caused by the pathogenic mutation was rescued by a second mutation located in a allosteric pathway\u00a0that spans from the nucleotide\u2010binding pocket to domain IV. This compensatory mutation restored proper nuclear localization of eIF6 (Tif6 in yeast). These findings reveal that the R1086Q mutation disrupts a structural communication network within Efl1, impairing the conformational dynamics required for its activity. The loss of this coordination likely underlies the ribosome maturation defects observed in SDS cases linked to EFL1, offering new insights into the molecular basis of the disease.\n                  <\/jats:p>","DOI":"10.1002\/pro.70504","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T13:40:57Z","timestamp":1773841257000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hydroxyl radical footprinting modification reveals an intradomain communication pathway in\n                    <scp>EFL1<\/scp>\n                    disrupted by a Shwachman\u2010Diamond syndrome\u2010associated mutation"],"prefix":"10.1002","volume":"35","author":[{"given":"Jonathan A.","family":"Z\u00fa\u00f1iga\u2010Dom\u00ednguez","sequence":"first","affiliation":[{"name":"Departamento de Qu\u00edmica de Biomacromol\u00e9culas, Instituto de Qu\u00edmica Universidad Nacional Aut\u00f3noma de M\u00e9xico  Ciudad de M\u00e9xico Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0780-1869","authenticated-orcid":false,"given":"Rohit","family":"Jain","sequence":"additional","affiliation":[{"name":"Center for Synchrotron Biosciences Case Western Reserve University, School of Medicine  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8910-3035","authenticated-orcid":false,"given":"Mart\u00edn","family":"Gonz\u00e1lez\u2010Andrade","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Facultad de Medicina Universidad Nacional Aut\u00f3noma de M\u00e9xico  Ciudad de M\u00e9xico Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6419-038X","authenticated-orcid":false,"given":"Erik R.","family":"Farquhar","sequence":"additional","affiliation":[{"name":"Center for Synchrotron Biosciences Case Western Reserve University, School of Medicine  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2991-6405","authenticated-orcid":false,"given":"Mark R.","family":"Chance","sequence":"additional","affiliation":[{"name":"Center for Synchrotron Biosciences Case Western Reserve University, School of Medicine  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6622-3686","authenticated-orcid":false,"given":"Abril","family":"Gijsbers","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica de Biomacromol\u00e9culas, Instituto de Qu\u00edmica Universidad Nacional Aut\u00f3noma de M\u00e9xico  Ciudad de M\u00e9xico Mexico"},{"name":"Departamento de Bioqu\u00edmica, Facultad de Medicina Universidad Nacional Aut\u00f3noma de M\u00e9xico  Ciudad de M\u00e9xico Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8945-7001","authenticated-orcid":false,"given":"Nuria","family":"S\u00e1nchez\u2010Puig","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica de Biomacromol\u00e9culas, Instituto de Qu\u00edmica Universidad Nacional Aut\u00f3noma de M\u00e9xico  Ciudad de M\u00e9xico Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.12.143"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1107\/S1600577519003576"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(10)70007-0"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.5.1453-1462.2001"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004380100548"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1062"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi060652l"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1107\/S1600577520009960"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16132392"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2019.1704883"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2022112699"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2011.06349.x"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2019.07.004"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.623011"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1107\/S1600576717007786"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.626275"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.06.077"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19124012"},{"key":"e_1_2_10_20_1","article-title":"Fluorescence anisotropy as a tool to study protein\u2010protein interactions","volume":"116","author":"Gijsbers A","year":"2016","journal-title":"J vis Exp"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e34301"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2015.06.010"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-10-6038-0_14"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06034-2"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2014.11.013"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2016.08.001"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1107\/S1600577521005026"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/jasms.3c00368"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11658-024-00674-7"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406218200"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz637"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3731"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-018-0078-y"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202051121"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpc.2019.02.003"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00438-021-01814-w"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1994"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.4153"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-10-178129"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ircmb.2015.07.002"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2025.169003"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1505297112"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12081141"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1993.tb17809.x"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20906"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00403-8"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2008.07.004"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi990516z"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2016-104366"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aap9714"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1101\/mcs.a003046"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2018893404"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.4161\/idp.24360"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-030222-113611"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1062023"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(99)01460-7"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.3112"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-062708-134043"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00213575"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.113.153197"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-04689-3"}],"container-title":["Protein Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pro.70504","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pro.70504","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pro.70504","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pro.70504","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T11:22:16Z","timestamp":1778325736000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pro.70504"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,18]]},"references-count":60,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/pro.70504"],"URL":"https:\/\/doi.org\/10.1002\/pro.70504","archive":["Portico"],"relation":{},"ISSN":["0961-8368","1469-896X"],"issn-type":[{"value":"0961-8368","type":"print"},{"value":"1469-896X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,18]]},"assertion":[{"value":"2025-10-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70504"}}