{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:59:36Z","timestamp":1790852376450,"version":"4.1.0"},"reference-count":38,"publisher":"Portland Press Ltd.","issue":"10","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome Trust","award":["321588\/Z\/24\/Z"],"award-info":[{"award-number":["321588\/Z\/24\/Z"]}]},{"name":"Wellcome Trust","award":["321588\/Z\/24\/Z"],"award-info":[{"award-number":["321588\/Z\/24\/Z"]}]},{"name":"Wellcome Trust","award":["321588\/Z\/24\/Z"],"award-info":[{"award-number":["321588\/Z\/24\/Z"]}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,10,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Innate immune signalling is uniquely driven through the formation of supramolecular organising centres (SMOCs), which couple receptor activation with downstream effector recruitment. The adaptor protein TRIF coordinates interferon, inflammatory, and cell death responses downstream of TLR3 and TLR4 activation, yet exactly how this protein drives such diverse outputs remains unresolved. Recent structural studies of recombinant TRIF, alongside single-molecule fluorescence imaging of endogenously expressed TRIF in live cells, reveal that TRIF assembles into complexes with heterogeneous size and morphology, with monomeric and low-order complexes associated with early-phase interferon signalling and mature, RIPK1-containing complexes associated with NF-\u03baB activation. This review explores how differences in the structural architecture of the TRIFosome, from TIR-mediated oligomerisation through to RHIM-mediated cross-linking, may underlie this divergence in signalling outcome. Finally, this review discusses the translational opportunities that coordinating scaffold assembly with downstream function presents, including structure-selective therapeutics capable of shifting the balance between TRIF\u2019s signalling outputs and novel diagnostics that could be built on TRIFosome heterogeneity as a molecular fingerprint of disease.<\/jats:p>","DOI":"10.1042\/bst20260704","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:45:18Z","timestamp":1790851518000},"page":"1387-1395","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["One adaptor, multiple outcomes: decoding TRIFosome heterogeneity"],"prefix":"10.1042","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5298-5994","authenticated-orcid":false,"given":"Prasanna","family":"Suresh","sequence":"first","affiliation":[{"name":"1Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5486-278X","authenticated-orcid":false,"given":"Yu\u00a0P.","family":"Zhang","sequence":"additional","affiliation":[{"name":"1Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2924-0038","authenticated-orcid":false,"given":"Clare","family":"Bryant","sequence":"additional","affiliation":[{"name":"2Department of Veterinary Medicine, University of Cambridge, Cambridge, U.K."},{"name":"3Department of Medicine, University of Cambridge, Cambridge, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7116-6954","authenticated-orcid":false,"given":"David","family":"Klenerman","sequence":"additional","affiliation":[{"name":"1Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"2026100106451088200_B1","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1038\/nri3757","article-title":"SMOCs: supramolecular organizing centres that control innate immunity","volume":"14","author":"Kagan","year":"2014","journal-title":"Nat. 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