Molecular mechanism of influenza A NS1-mediated TRIM25 recognition and inhibition.
Molecular mechanism of influenza A NS1-mediated TRIM25 recognition and inhibition.
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DOI：
10.1038/s41467-018-04214-8
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发表时间：
2018-05-08
影响因子：
16.6
通讯作者：
Rittinger K
中科院分区：
文献类型：
--
作者：
Koliopoulos MG;Lethier M;van der Veen AG;Haubrich K;Hennig J;Kowalinski E;Stevens RV;Martin SR;Reis e Sousa C;Cusack S;Rittinger K
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. NS1 of influenza A virus inhibits TRIM25 activity, which is an E3 ligase important for induction of the interferon response. Here, Koliopoulos et al. present structures of TRIM25 and NS1 and show how NS1 binding interferes with substrate recognition of TRIM25.
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DOI：
10.1042/bj20121425
发表时间：
2013-12-01
期刊：
The Biochemical journal
影响因子：
--
作者：
D'Cruz AA;Kershaw NJ;Chiang JJ;Wang MK;Nicola NA;Babon JJ;Gack MU;Nicholson SE
通讯作者：
Nicholson SE
影响因子：
64.8
作者：
Jiang, Fuguo;Ramanathan, Anand;Miller, Matthew T.;Tang, Guo-Qing;Gale, Michael, Jr.;Patel, Smita S.;Marcotrigiano, Joseph
通讯作者：
Marcotrigiano, Joseph
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
2.6
作者：
Carvalho, Andreia F.;Pinto, Manuel P.;Azevedo, Jorge E.
通讯作者：
Azevedo, Jorge E.
影响因子：
6.1
作者：
Konarev, PV;Volkov, VV;Svergun, DI
通讯作者：
Svergun, DI