6FLM

Crystal structure of the human TRIM25 PRYSPRY domain

Summary for 6FLM

• Entry DOI: 10.2210/pdb6flm/pdb
• Descriptor: E3 ubiquitin/ISG15 ligase TRIM25, SULFATE ION, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: pryspry domain, trim protein, e3 ligase, protein binding
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : Q14258
• Total number of polymer chains: 3
• Total formula weight: 69369.84

Authors

Cusack, S.,Kowalinski, E. (deposition date: 2018-01-26, release date: 2018-05-23, Last modification date: 2024-05-08)

Primary citation

Koliopoulos, M.G.,Lethier, M.,van der Veen, A.G.,Haubrich, K.,Hennig, J.,Kowalinski, E.,Stevens, R.V.,Martin, S.R.,Reis E Sousa, C.,Cusack, S.,Rittinger, K.
Molecular mechanism of influenza A NS1-mediated TRIM25 recognition and inhibition.
Nat Commun, 9:1820-1820, 2018

PubMed 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.

PubMed: 29739942
DOI: 10.1038/s41467-018-04214-8

Experimental method

X-RAY DIFFRACTION (2.009 Å)