Duplicated TLR5 of zebrafish functions as a heterodimeric receptor.
Proc Natl Acad Sci U S A
; 115(14): E3221-E3229, 2018 04 03.
Article
em En
| MEDLINE
| ID: mdl-29555749
ABSTRACT
Toll-like receptor 5 (TLR5) of mammals, birds, and reptiles detects bacterial flagellin and signals as a homodimeric complex. Structural studies using truncated TLR5b of zebrafish confirm the homodimeric TLR5-flagellin interaction. Here we provide evidence that zebrafish (Danio rerio) TLR5 unexpectedly signals as a heterodimer composed of the duplicated gene products drTLR5b and drTLR5a. Flagellin-induced signaling by the zebrafish TLR5 heterodimer increased in the presence of the TLR trafficking chaperone UNC93B1. Targeted exchange of drTLR5b and drTLR5a regions revealed that TLR5 activation needs a heterodimeric configuration of the receptor ectodomain and cytoplasmic domain, consistent with ligand-induced changes in receptor conformation. Structure-guided substitution of the presumed principal flagellin-binding site in human TLR5 with corresponding zebrafish TLR5 residues abrogated human TLR5 activation, indicating a species-specific TLR5-flagellin interaction. Our findings indicate that the duplicated TLR5 of zebrafish underwent subfunctionalization through concerted coevolution to form a unique heterodimeric flagellin receptor that operates fundamentally differently from TLR5 of other species.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Duplicação Gênica
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Receptor 5 Toll-Like
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Flagelina
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Holanda