AI Article Synopsis
- RIG-I is a protein that helps detect viral infections by triggering the production of type I interferon to activate the immune response.
- The protein TRIM25 modifies RIG-I with specific ubiquitin chains, which is essential for activating the immune signaling pathway against viruses.
- The influenza A virus's NS1 protein disrupts TRIM25's function, preventing RIG-I from properly tagging substrates for immune response, which helps the virus evade the host's immune defenses.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940772 | PMC |
| http://dx.doi.org/10.1038/s41467-018-04214-8 | DOI Listing |
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