bei Google ScholarTitelangaben
Koliopoulos, Marios G. ; Lethier, Mathilde ; van der Veen, Annemarthe G. ; Haubrich, Kevin ; Hennig, Janosch ; Kowalinski, Eva ; Stevens, Rebecca V. ; Martin, Stephen R. ; Reis e Sousa, Caetano ; Cusack, Stephen ; Rittinger, Katrin:
Molecular mechanism of influenza A NS1-mediated TRIM25 recognition and inhibition.
In: Nature Communications.
Bd. 9
(2018)
Heft 1
.
- No. 1820.
ISSN 2041-1723
DOI: https://doi.org/10.1038/s41467-018-04214-8
Abstract
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.