Imperial College London
Professor Caetano Reis e Sousa

ProfessorCaetanoReis e Sousa

Faculty of Medicine, Department of Immunology and Inflammation

Visiting Professor
 
 
 
//

Contact

 

c.reisesousa

 
 
//

Location

 

Wright Fleming WingSt Mary's Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Koliopoulos:2018:10.1038/s41467-018-04214-8,
author = {Koliopoulos, MG and Lethier, M and van, der Veen AG and Haubrich, K and Hennig, J and Kowalinski, E and Stevens, RV and Martin, SR and Reis, E Sousa C and Cusack, S and Rittinger, K},
doi = {10.1038/s41467-018-04214-8},
journal = {Nature Communications},
title = {Molecular mechanism of influenza A NS1-mediated TRIM25 recognition and inhibition},
url = {http://dx.doi.org/10.1038/s41467-018-04214-8},
volume = {9},
year = {2018}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Koliopoulos,MG
AU  - Lethier,M
AU  - van,der Veen AG
AU  - Haubrich,K
AU  - Hennig,J
AU  - Kowalinski,E
AU  - Stevens,RV
AU  - Martin,SR
AU  - Reis,E Sousa C
AU  - Cusack,S
AU  - Rittinger,K
DO  - 10.1038/s41467-018-04214-8
PY  - 2018///
SN  - 2041-1723
TI  - Molecular mechanism of influenza A NS1-mediated TRIM25 recognition and inhibition
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-018-04214-8
UR  - https://www.ncbi.nlm.nih.gov/pubmed/29739942
UR  - http://hdl.handle.net/10044/1/59287
VL  - 9
ER  -
Download