6MYD

Structure of zebrafish TRAF6 in complex with STING CTT

Summary for 6MYD

• Entry DOI: 10.2210/pdb6myd/pdb
• Descriptor: TNF receptor-associated factor 6, STING CTT, Transmembrane protein 173, SULFATE ION, ... (4 entities in total)
• Functional Keywords: innate immunity, sting, nf-kappab, traf6, tmem173, immune system
• Biological source: Danio rerio (Zebrafish); More
• Total number of polymer chains: 4
• Total formula weight: 38835.93

Authors

de Oliveira Mann, C.C.,Orzalli, M.H.,King, D.S.,Kagan, J.C.,Lee, A.S.Y.,Kranzusch, P.J. (deposition date: 2018-11-01, release date: 2019-05-01, Last modification date: 2023-10-11)

Primary citation

de Oliveira Mann, C.C.,Orzalli, M.H.,King, D.S.,Kagan, J.C.,Lee, A.S.Y.,Kranzusch, P.J.
Modular Architecture of the STING C-Terminal Tail Allows Interferon and NF-kappa B Signaling Adaptation.
Cell Rep, 27:1165-1175.e5, 2019

PubMed Abstract: Stimulator 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-κB-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-κB 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.

PubMed: 31018131
DOI: 10.1016/j.celrep.2019.03.098

Experimental method

X-RAY DIFFRACTION (1.399 Å)