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one of ten human TLRs, recognizes lipoproteins that are anchored to the bacterial membrane by lipid chains covalently dimerization (Jin et al., 2007). Double-stranded RNA induces ho-modimerization of TLR3 by interacting with its lateral surfaces (Liu et al., 2008). TLR4 does not directly interact with ligands;attached to conserved N-terminal cysteines (Hantke and Braun, 1973). Lipoproteins fromGram-negative bacteria have three lipid chains; two of them are attached by ester bonds to a glycerol instead, it forms a heterodimer with another protein, MD-2, and uses a pocket in MD-2 to interact with the LPS of Gram-negative bacteria (Kim et al., 2007b; Ohto et al., 2007; Park et al., 2009).blocked by two phenylalanines. Simultaneous muta-tion of these phenylalanines made TLR2-TLR6 fully responsive not only to diacylated but also to triacy-lated lipopeptides. Second, the hydrophobic dimer-ization 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