{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T16:41:03Z","timestamp":1784133663030,"version":"3.55.0"},"reference-count":87,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T00:00:00Z","timestamp":1697155200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p>\n                    Invasion of brain endothelium protein A (IbeA) is a virulence factor specific to pathogenic\n                    <jats:italic>Escherichia\u2009coli.<\/jats:italic>\n                    Originally identified in the K1 strain causing neonatal meningitis, it was more recently found in avian pathogenic\n                    <jats:italic>Escherichia\u2009coli<\/jats:italic>\n                    (APEC) and adherent invasive\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    (AIEC). In these bacteria, IbeA facilitates host cell invasion and intracellular survival, in particular, under harsh conditions like oxidative stress. Furthermore, IbeA from AIEC contributes to intramacrophage survival and replication, thus enhancing the inflammatory response within the intestine. Therefore, this factor is a promising drug target for anti\u2010AIEC strategies in the context of Crohn's disease. Despite such an important role, the biological function of IbeA remains largely unknown. In particular, its exact nature and cellular localization, i.e., membrane\u2010bound invasin versus cytosolic factor, are still of debate. Here, we developed an efficient protocol for recombinant expression of IbeA under native conditions and demonstrated that IbeA from AIEC is a soluble, homodimeric flavoprotein. Using mass spectrometry and tryptophan fluorescence measurements, we further showed that IbeA preferentially binds flavin adenine dinucleotide (FAD), with an affinity in the one\u2010hundred nanomolar range and optimal binding under reducing conditions. 3D\u2010modeling with AlphaFold revealed that IbeA shares strong structural homology with FAD\u2010dependent oxidoreductases. Finally, we used ligand docking, mutational analyses, and molecular dynamics simulations to identify the FAD binding pocket within IbeA and characterize possible conformational changes occurring upon ligand binding. Overall, we suggest that the role of IbeA in the survival of AIEC within host cells, notably macrophages, is linked to modulation of redox processes.\n                  <\/jats:p>","DOI":"10.1111\/febs.16969","type":"journal-article","created":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T05:17:21Z","timestamp":1696310241000},"page":"177-203","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The IbeA protein from adherent invasive\n                    <i>Escherichia coli<\/i>\n                    is\u00a0a flavoprotein sharing structural homology with FAD\u2010dependent oxidoreductases"],"prefix":"10.1111","volume":"291","author":[{"given":"Th\u00e9o","family":"Paris","sequence":"first","affiliation":[{"name":"LPHI Univ. Montpellier, CNRS, INSERM  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agneta","family":"Kiss","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, CEA, CNRS, IBS  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Signor","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, CEA, CNRS, IBS  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges","family":"Lutfalla","sequence":"additional","affiliation":[{"name":"LPHI Univ. Montpellier, CNRS, INSERM  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7860-3464","authenticated-orcid":false,"given":"Micka\u00ebl","family":"Blaise","sequence":"additional","affiliation":[{"name":"IRIM Univ. Montpellier, CNRS  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Boeri Erba","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, CEA, CNRS, IBS  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Chaloin","sequence":"additional","affiliation":[{"name":"IRIM Univ. Montpellier, CNRS  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3650-8012","authenticated-orcid":false,"given":"Laure","family":"Yatime","sequence":"additional","affiliation":[{"name":"LPHI Univ. Montpellier, CNRS, INSERM  France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.04.061"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13099-018-0248-7"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21899"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0b013e3182a38a92"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2012.01768.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.12.010"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.157013"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2957"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2021.01.002"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2015-311059"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.00108"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.9.5529-5537.2001"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.00742"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2011.156"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-02161-7"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics9050251"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44632"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000183"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08529"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/567929"},{"key":"e_1_2_10_22_1","first-page":"279","article-title":"The role of major virulence factors and pathogenicityof adherent\u2010invasive Escherichia coli in patients with Crohn's disease","volume":"15","author":"Abdelhalim KA","year":"2020","journal-title":"Prz Gastroenterol"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01298-15"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.03003-14"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.11.4470-4475.1995"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1086\/319290"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2007.06213.x"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.10.091"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00430-006-0034-x"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035862"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04637-3"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2006.08.016"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.27809-0"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00821-10"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00089-12"},{"key":"e_1_2_10_36_1","unstructured":"CiezaRJ(2015)The invasin IbeA and its role in adherent\u2010invasiveEscherichia coli(AIEC) pathogenesis. PhD Thesis University of Texas Medical Branch USA."},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1110\/ps.12801"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(87)90191-4"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-021-01156-3"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.4519"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444904026460"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2010.09.032"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2011.04.002"},{"key":"e_1_2_10_44_1","unstructured":"EvansR O'NeillM PritzelA AntropovaN SeniorA GreenT \u017d\u00eddekA BatesR BlackwellS YimJet\u00a0al. (2021)Protein complex prediction with AlphaFold\u2010Multimer. Bioinformatics."},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2007.05.022"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010877"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00334-08"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0137131"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22306-w"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-11-667"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24021740"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01769-14"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21113797"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.6.1937-1944.2005"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(89)90298-2"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi900411a"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.5b00174"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2015.09.006"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvj118"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsos.211903"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-019-00250-8"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00414-7"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5560051122"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks396"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1107\/S1744309111027990"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.2661"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7759-8_9"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2020.103799"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0177161"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac0110552"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac061039a"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac300056a"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2020.107689"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.3253"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03819-2"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj8754"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.23354"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1996.0897"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910007493"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv315"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3280"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.1063\/5.0014475"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.445869"},{"key":"e_1_2_10_85_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.464397"},{"key":"e_1_2_10_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/0263-7855(96)00018-5"},{"key":"e_1_2_10_87_1","unstructured":"GowersR LinkeM BarnoudJ ReddyT MeloM SeylerS Doma\u0144skiJ DotsonD BuchouxS KenneyIet\u00a0al. (2016)MDAnalysis: A Python Package for the Rapid Analysis of Molecular Dynamics Simulations pp. 98\u2013105. Austin TX. doi:10.25080\/Majora\u2010629e541a\u201000e"},{"key":"e_1_2_10_88_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btab187"}],"container-title":["The FEBS Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.16969","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T05:19:01Z","timestamp":1705555141000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1111\/febs.16969"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,13]]},"references-count":87,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1111\/febs.16969"],"URL":"https:\/\/doi.org\/10.1111\/febs.16969","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/FEBS.16969\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/FEBS.16969\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/FEBS.16969\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/FEBS.16969\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/FEBS.16969\/v2\/response1","asserted-by":"object"}]},"ISSN":["1742-464X","1742-4658"],"issn-type":[{"value":"1742-464X","type":"print"},{"value":"1742-4658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,13]]},"assertion":[{"value":"2023-06-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}