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dc.contributor.authorVe, Thomas
dc.contributor.authorVajjhala, Parimala R.
dc.contributor.authorHedger, Andrew
dc.contributor.authorCroll, Tristan I.
dc.contributor.authorDiMaio, Frank
dc.contributor.authorHorsefield, Shane
dc.contributor.authorYu, Xiong
dc.contributor.authorLavrencic, Peter
dc.contributor.authorHassan, Zahid
dc.contributor.authorMorgan, Garry P.
dc.contributor.authorMansell, Ashley
dc.contributor.authorMobli, Mehdi
dc.contributor.authorO'Carroll, Ailis
dc.contributor.authorChauvin, Brieuc
dc.contributor.authorGambin, Yann
dc.contributor.authorSierecki, Emma
dc.contributor.authorLandsberg, Michael J.
dc.contributor.authorStacey, Katryn J,
dc.contributor.authorEgelman, Edward H.
dc.contributor.authorKobe, B.
dc.date.accessioned2018-01-05T02:17:53Z
dc.date.available2018-01-05T02:17:53Z
dc.date.issued2017
dc.identifier.issn1545-9993en_US
dc.identifier.doi10.1038/nsmb.3444en_US
dc.identifier.urihttp://hdl.handle.net/10072/360730
dc.description.abstractToll-like receptor (TLR) signaling is a key innate immunity response to pathogens. Recruitment of signaling adapters such as MAL (TIRAP) and MyD88 to the TLRs requires Toll/interleukin-1 receptor (TIR)-domain interactions, which remain structurally elusive. Here we show that MAL TIR domains spontaneously and reversibly form filaments in vitro. They also form cofilaments with TLR4 TIR domains and induce formation of MyD88 assemblies. A 7-Å-resolution cryo-EM structure reveals a stable MAL protofilament consisting of two parallel strands of TIR-domain subunits in a BB-loop-mediated head-to-tail arrangement. Interface residues that are important for the interaction are conserved among different TIR domains. Although large filaments of TLR4, MAL or MyD88 are unlikely to form during cellular signaling, structure-guided mutagenesis, combined with in vivo interaction assays, demonstrated that the MAL interactions defined within the filament represent a template for a conserved mode of TIR-domain interaction involved in both TLR and interleukin-1 receptor signaling.en_US
dc.description.peerreviewedYesen_US
dc.languageEnglishen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofpagefrom743en_US
dc.relation.ispartofpageto751en_US
dc.relation.ispartofjournalNature Structural and Molecular Biologyen_US
dc.relation.ispartofvolume24en_US
dc.subject.fieldofresearchBiochemistry and Cell Biology not elsewhere classifieden_US
dc.subject.fieldofresearchcode060199en_US
dc.titleStructural basis of TIR-domain-assembly formation in MAL- and MyD88-dependent TLR4 signalingen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.facultyOffice of the Snr Dep Vice Chancellor, Institute for Glycomicsen_US
gro.hasfulltextNo Full Text


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