tetano
Editor, Senior Moderator
Nat Commun. 2018 May 8;9(1):1820. doi: 10.1038/s41467-018-04214-8.
[h=1]Molecular mechanism of influenza A NS1-mediated TRIM25 recognition and inhibition.[/h] Koliopoulos MG[SUP]1[/SUP], Lethier M[SUP]2[/SUP], van der Veen AG[SUP]3[/SUP], Haubrich K[SUP]4[/SUP], Hennig J[SUP]4[/SUP], Kowalinski E[SUP]2[/SUP], Stevens RV[SUP]1[/SUP], Martin SR[SUP]5[/SUP], Reis E Sousa C[SUP]3[/SUP], Cusack S[SUP]2[/SUP], Rittinger K[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] RIG-I is a viral RNA sensor that induces the production of type I interferon (IFN) in response to infection with a variety of viruses. Modification of RIG-I with K63-linked poly-ubiquitin chains, synthesised by TRIM25, is crucial for activation of the RIG-I/MAVS signalling pathway. TRIM25 activity is targeted by influenza A virus non-structural protein 1 (NS1) to suppress IFN production and prevent an efficient host immune response. Here we present structures of the human TRIM25 coiled-coil-PRYSPRY module and of complexes between the TRIM25 coiled-coil domain and NS1. These structures show that binding of NS1 interferes with the correct positioning of the PRYSPRY domain of TRIM25 required for substrate ubiquitination and provide a mechanistic explanation for how NS1 suppresses RIG-I ubiquitination and hence downstream signalling. In contrast, the formation of unanchored K63-linked poly-ubiquitin chains is unchanged by NS1 binding, indicating that RING dimerisation of TRIM25 is not affected by NS1.
PMID: 29739942 PMCID: PMC5940772 DOI: 10.1038/s41467-018-04214-8
Free PMC Article
[h=1]Molecular mechanism of influenza A NS1-mediated TRIM25 recognition and inhibition.[/h] Koliopoulos MG[SUP]1[/SUP], Lethier M[SUP]2[/SUP], van der Veen AG[SUP]3[/SUP], Haubrich K[SUP]4[/SUP], Hennig J[SUP]4[/SUP], Kowalinski E[SUP]2[/SUP], Stevens RV[SUP]1[/SUP], Martin SR[SUP]5[/SUP], Reis E Sousa C[SUP]3[/SUP], Cusack S[SUP]2[/SUP], Rittinger K[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] RIG-I is a viral RNA sensor that induces the production of type I interferon (IFN) in response to infection with a variety of viruses. Modification of RIG-I with K63-linked poly-ubiquitin chains, synthesised by TRIM25, is crucial for activation of the RIG-I/MAVS signalling pathway. TRIM25 activity is targeted by influenza A virus non-structural protein 1 (NS1) to suppress IFN production and prevent an efficient host immune response. Here we present structures of the human TRIM25 coiled-coil-PRYSPRY module and of complexes between the TRIM25 coiled-coil domain and NS1. These structures show that binding of NS1 interferes with the correct positioning of the PRYSPRY domain of TRIM25 required for substrate ubiquitination and provide a mechanistic explanation for how NS1 suppresses RIG-I ubiquitination and hence downstream signalling. In contrast, the formation of unanchored K63-linked poly-ubiquitin chains is unchanged by NS1 binding, indicating that RING dimerisation of TRIM25 is not affected by NS1.
PMID: 29739942 PMCID: PMC5940772 DOI: 10.1038/s41467-018-04214-8
Free PMC Article