Structure of vaccinia virus A46, an inhibitor of TLR4 signaling pathway, shows the conformation of VIPER motif.
Protein Sci
; 23(7): 906-14, 2014 Jul.
Article
in En
| MEDLINE
| ID: mdl-24723367
ABSTRACT
Vaccinia virus (VACV) encodes many proteins that interfere with the host immune system. Vaccinia virus A46 protein specifically targets the BB-loop motif of TIR-domain-containing proteins to disrupt receptoradaptor (e.g., TLR4MAL and TLR4TRAM) interactions of the toll-like receptor signaling. The crystal structure of A46 (75-227) determined at 2.58 Å resolution showed that A46 formed a homodimer and adopted a Bcl-2-like fold similar to other VACV proteins such as A52, B14, and K7. Our structure also revealed that VIPER (viral inhibitory peptide of TLR4) motif resides in the α1-helix and six residues of the VIPER region were exposed to surface for binding to target proteins. In vitro binding assays between wild type and six mutants A46 (75-227) and full-length MAL identified critical residues in the VIPER motif. Computational modeling of the A46MAL complex structure showed that the VIPER region of A46 and AB loop of MAL protein formed a major binding interface. In summary, A46 is a homodimer with a Bcl-2-like fold and VIPER motif is believed to be involved in the interaction with MAL protein based on our binding assays.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Viral Proteins
/
Toll-Like Receptor 4
/
Myelin and Lymphocyte-Associated Proteolipid Proteins
Limits:
Humans
Language:
En
Journal:
Protein Sci
Journal subject:
BIOQUIMICA
Year:
2014
Document type:
Article