6FLM

Crystal structure of the human TRIM25 PRYSPRY domain

6FLM の概要

• エントリーDOI: 10.2210/pdb6flm/pdb
• 分子名称: E3 ubiquitin/ISG15 ligase TRIM25, SULFATE ION, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: pryspry domain, trim protein, e3 ligase, protein binding
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm : Q14258
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 69369.84

構造登録者

Cusack, S.,Kowalinski, E. (登録日: 2018-01-26, 公開日: 2018-05-23, 最終更新日: 2024-05-08)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.009 Å)