{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T18:05:40Z","timestamp":1781028340821,"version":"3.54.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1014311","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000}}],"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    NOD1 and NOD2, founding members of the NOD-like receptor (NLR) family, play a crucial role in host defense against bacterial infections. Recognition of peptidoglycan-derived ligands triggers ATP-dependent oligomerization of the NACHT domain, exposing the CARD domains that recruit the adaptor protein RIP2 via CARD\u2013CARD interactions to activate the NF-\u03baB signaling cascade. Although NOD1\/2-RIP2 interactions and RIP2\n                    <jats:sup>CARD<\/jats:sup>\n                    filament assembly are established, the precise interfaces that stabilize hetero\u2013CARD filaments remain poorly defined. Here, we integrate\n                    <jats:italic>in silico<\/jats:italic>\n                    structural modeling with molecular dynamics (MD) simulations to elucidate structurally compatible arrangements of NOD1\u2013RIP2 and NOD2\u2013RIP2 hetero\u2013CARD filaments. Our results reveal that NOD1\n                    <jats:sup>CARD<\/jats:sup>\n                    subunits form a structurally compatible homomeric scaffold via canonical (type-I\u2013III) interfaces, accommodating multiple tiers of RIP2\n                    <jats:sup>CARD<\/jats:sup>\n                    rings at both filament termini. Meanwhile, the NOD2 tandem CARDs adopt multiple discrete conformations, reflecting a more intricate structural mechanism. In stable filament conformations, tandem CARDs converge at the type-II interface, with RIP2\n                    <jats:sup>CARD<\/jats:sup>\n                    rings stacking onto CARDa (top-down) and CARDb (bottom-up) interfaces, highlighting the structural role of NOD2\n                    <jats:sup>CARDb<\/jats:sup>\n                    in RIP2-mediated CARD\u2013CARD interaction.\n                    <jats:italic>In silico<\/jats:italic>\n                    mutagenesis, involving charge-reversal and alanine scanning of key interfacial residues, disrupts NOD1\u2013RIP2 and NOD2\u2013RIP2 interactions at both top-down and bottom-up interfaces, leading to rapid interface destabilization within 0.1\u20130.4 \u03bcs of simulation. Together, these results reveal conserved and receptor-specific mechanisms governing NOD1\/2\u2013RIP2 CARD\u2013CARD interactions and provide deeper structural and dynamic insights into the complex structural mechanisms for NLR-mediated inflammatory signaling.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1014311","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T17:39:52Z","timestamp":1780076392000},"page":"e1014311","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structural and dynamic basis of NOD2 tandem CARD association and NOD1\/2\u2013RIP2 signaling complexes"],"prefix":"10.1371","volume":"22","author":[{"given":"Jitendra","family":"Maharana","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5561-1891","authenticated-orcid":true,"given":"Aritra","family":"Bej","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9302-322X","authenticated-orcid":true,"given":"Debasish","family":"Biswal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debashis","family":"Panda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1062-4215","authenticated-orcid":true,"given":"Arjun","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"issue":"9","key":"pcbi.1014311.ref001","first-page":"4475","article-title":"Approaching the asymptote? 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