PUBLICATION
Duplicated TLR5 of zebrafish functions as a heterodimeric receptor
- Authors
- Voogdt, C.G.P., Wagenaar, J.A., van Putten, J.P.M.
- ID
- ZDB-PUB-180321-19
- Date
- 2018
- Source
- Proceedings of the National Academy of Sciences of the United States of America 115(14): E3221-E3229 (Journal)
- Registered Authors
- Keywords
- TLR5, flagellin, heterodimer, subfunctionalization, zebrafish
- MeSH Terms
-
- Protein Conformation
- Flagellin/metabolism*
- Models, Molecular
- HeLa Cells
- Protein Multimerization
- PubMed
- 29555749 Full text @ Proc. Natl. Acad. Sci. USA
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.
Genes / Markers
Figure Gallery (4 images)
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping