Title : Recognition of lipopeptide patterns by
Toll-like receptor 2-
Toll-like receptor 6 heterodimer
Abstract :
- Toll-like receptor 2 ( TLR2 ) initiates potent immune responses by recognizing diacylated and triacylated lipopeptides
- Its ligand specificity is controlled by whether it heterodimerizes with TLR1 or TLR6
- We have determined the crystal structures of TLR2- TLR6-diacylated lipopeptide , TLR2-lipoteichoic acid, and TLR2-PE-DTPA complexes
- PE-DTPA, 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-diethylenetriaminepentaacetic acid, is a synthetic phospholipid derivative
- Two major factors contribute to the ligand specificity of TLR2- TLR1 or TLR2- TLR6 heterodimers
- First, the lipid channel of TLR6 is blocked by two phenylalanines
- Simultaneous mutation of these phenylalanines made TLR2- TLR6 fully responsive not only to diacylated but also to triacylated lipopeptides
- Second, the hydrophobic dimerization interface of TLR2- TLR6 is increased by 80%, which compensates for the lack of amide lipid interaction between the lipopeptide and TLR2- TLR6
- The structures of the TLR2-lipoteichoic acid and the TLR2-PE-DTPA complexes demonstrate that a precise interaction pattern of the head group is essential for a robust immune response by TLR2 heterodimers