Structural highlights
Function[TRAF6_DANRE] E3 ubiquitin-protein ligase that mediates ubiquitination of proteins. Adapter protein that seems to play a role in signal transduction. Publication Abstract from PubMedStimulator of interferon genes (STING) is a key regulator of type I interferon and pro-inflammatory responses during infection, cellular stress, and cancer. Here, we reveal a mechanism for how STING balances activation of IRF3- and NF-kappaB-dependent transcription and discover that acquisition of discrete signaling modules in the vertebrate STING C-terminal tail (CTT) shapes downstream immunity. As a defining example, we identify a motif appended to the CTT of zebrafish STING that inverts the typical vertebrate signaling response and results in dramatic NF-kappaB activation and weak IRF3-interferon signaling. We determine a co-crystal structure that explains how this CTT sequence recruits TRAF6 as a new binding partner and demonstrate that the minimal motif is sufficient to reprogram human STING and immune activation in macrophage cells. Together, our results define the STING CTT as a linear signaling hub that can acquire modular motifs to readily adapt downstream immunity. Modular Architecture of the STING C-Terminal Tail Allows Interferon and NF-kappaB Signaling Adaptation.,de Oliveira Mann CC, Orzalli MH, King DS, Kagan JC, Lee ASY, Kranzusch PJ Cell Rep. 2019 Apr 23;27(4):1165-1175.e5. doi: 10.1016/j.celrep.2019.03.098. PMID:31018131[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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