{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:51:28Z","timestamp":1791312688609,"version":"4.3.1"},"reference-count":65,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["2022PJKF88"],"award-info":[{"award-number":["2022PJKF88"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["0225X2FS5"],"award-info":[{"award-number":["0225X2FS5"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["IR0000011"],"award-info":[{"award-number":["IR0000011"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020581","name":"Fondazione AIRC per la ricerca sul cancro ETS","doi-asserted-by":"publisher","award":["25728"],"award-info":[{"award-number":["25728"]}],"id":[{"id":"10.13039\/100020581","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tumor necrosis factor receptor\u2010associated factor 2 (TRAF2) is a key adaptor in TNF receptor\u2010signaling that operates as a trimeric assembly. Here we investigate the structural and functional properties of a TRAF2 construct spanning the trimerization and receptor\u2010binding domains (TRAF2\u2010NC, residues 266\u2013501). According to SAXS data, under physiological conditions, TRAF2\u2010NC preserves a stable trimeric structure with signs of conformational flexibility. Conversely, in a mildly acidic environment (pH\u20095.7), the protein adopts a less compact and more heterogeneous conformation. In this condition, fluorescence energy transfer measurements reveal an increased membrane\u2010binding propensity in the presence of ganglioside GM1. Together, these results indicate that TRAF2 oligomerization is modulated by pH\u2010dependent conformational changes, suggesting that increased structural flexibility and partial exposure of hydrophobic regions facilitate membrane association under stress conditions, and providing a mechanistic link between structural dynamics and TRAF2 function.<\/jats:p>","DOI":"10.1002\/pro.70817","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:05:02Z","timestamp":1791309902000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structural dynamics and\n                    <scp>pH<\/scp>\n                    \u2010regulated membrane binding of the\n                    <scp>TRAF2<\/scp>\n                    \u2010\n                    <scp>NC<\/scp>\n                    trimer"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9753-3572","authenticated-orcid":false,"given":"Federica","family":"Cossu","sequence":"first","affiliation":[{"name":"Institute of Biophysics, National Research Council (IBF\u2010CNR)  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5555-1048","authenticated-orcid":false,"given":"Serena","family":"Virili","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine Tor Vergata University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4835-5117","authenticated-orcid":false,"given":"Bianca","family":"Braggiotti","sequence":"additional","affiliation":[{"name":"Institute of Biophysics, National Research Council (IBF\u2010CNR)  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4701-4421","authenticated-orcid":false,"given":"Francesco","family":"Bon\u00ec","sequence":"additional","affiliation":[{"name":"Institute of Biophysics, National Research Council (IBF\u2010CNR)  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5702-3674","authenticated-orcid":false,"given":"Federico","family":"Ballabio","sequence":"additional","affiliation":[{"name":"Institute of Biophysics, National Research Council (IBF\u2010CNR)  Milan Italy"},{"name":"Institute of Structural Biology, Molecular Targets and Therapeutics Center Helmholtz Munich \u2010 Deutsches Forschungszentrum F\u00fcr Gesundheit Und Umwelt (GmbH)  Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6449-0596","authenticated-orcid":false,"given":"Toni","family":"Giorgino","sequence":"additional","affiliation":[{"name":"Institute of Biophysics, National Research Council (IBF\u2010CNR)  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6098-3991","authenticated-orcid":false,"given":"Mario","family":"Milani","sequence":"additional","affiliation":[{"name":"Institute of Biophysics, National Research Council (IBF\u2010CNR)  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3772-9463","authenticated-orcid":false,"given":"Giampiero","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine Tor Vergata University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almerinda","family":"Di Venere","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine Tor Vergata University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5968-8386","authenticated-orcid":false,"given":"Eloise","family":"Mastrangelo","sequence":"additional","affiliation":[{"name":"Institute of Biophysics, National Research Council (IBF\u2010CNR)  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07487-w"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-025-07609-w"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.3c00864"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2016.03.009"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/371854"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2014.08.011"},{"key":"e_1_2_8_8_1","volume-title":"Biophysical chemistry part I: the conformation of biological macromolecules","author":"Cantor CR","year":"1980"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.5b00674"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2017.05.003"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1071924"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2021.11.034"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.0c00518"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.14530"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2023.106508"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.529"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22115871"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/bab.1615"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1515\/bmc-2022-0031"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom15111626"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1107\/S1600576717007786"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1107\/S2059798317005745"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4067"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.8016"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aax5647"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-1130-2_13"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4757-3061-6_11"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(84)84043-6"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.5b00935"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2008.09.013"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-023-01164-7"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-61271-6"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-013-9644-8"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1107\/S1600576720013412"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.15.8408"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky497"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/sym14040720"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2020.1719202"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.133371"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/ct100578z"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5CP04540A"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btx846"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01999"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12272-021-01330-w"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/19110"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80889-2"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14191"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R200021-JLR200"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.09.034"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22031334"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90532-0"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14164055"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/35036052"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889892001663"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(99)77443-6"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1063\/5.0251501"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20291"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.072256"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401189"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a008698"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00365"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80334-2"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02618"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.569684"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.03.009"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prmcm.2023.100265"}],"container-title":["Protein Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pro.70817","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pro.70817","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pro.70817","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:05:04Z","timestamp":1791309904000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pro.70817"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,6]]},"references-count":65,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["10.1002\/pro.70817"],"URL":"https:\/\/doi.org\/10.1002\/pro.70817","archive":["Portico"],"relation":{},"ISSN":["0961-8368","1469-896X"],"issn-type":[{"value":"0961-8368","type":"print"},{"value":"1469-896X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,6]]},"assertion":[{"value":"2026-05-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70817"}}