Title :
Toll-like receptor 5 forms asymmetric
dimers in the absence of flagellin
Abstract :
- The structure of full-length human TLR5 determined by electron microscopy single-particle image reconstruction at 26Å resolution shows that TLR5 forms an asymmetric homodimer via ectodomain interactions
- The structure shows that like TLR9 , TLR5 dimerizes in the absence of ligand
- The asymmetry of the dimer suggests that TLR5 may recognize two flagellin molecules cooperatively to establish an optimal flagellin response threshold
- A TLR5 homology model was generated and fitted into the electron microscopy structure
- All seven predicted N-linked glycosylation sites are exposed on the molecular surface, away from the dimer interface
- Glycosylation at the first five sites was confirmed by tandem mass spectrometry
- Two aspartate residues proposed to interact with flagellin ( Asp294 and Asp366 ) are sterically occluded by a glycan at position 342
- In contrast, the central region of the ectodomains near the dimer interface is unobstructed by glycans
- Ligand binding in this region would be consistent with the ligand binding sites of other TLRs
Output (sent_index, trigger,
protein,
sugar,
site):
- 6. Glycosylation, , -, -, sites
- 7. position, , -, a glycan, position 342
Output(Part-Of) (sent_index,
protein,
site):
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):