Table 4.
Correlations between ligand orientation, its position and function are listed for available crystal structures. First two columns show the complexes with the ligands. Third column shows their interrelatedness according to position and effects. Last column shows the relative orientation of the glucosamine backbone of LPS, lipid A or lipid IVa. LPS in 3FXI [8] serves as a reference with its backbone orientation in the MD-2 pocket arbitrarily designated as “fit”, and the inverse orientation of the di-phosphorylated di-glucosmine backbone i.e. the binding mode in an 180° horizontal backbone rotation is termed “flipped”. The corresponding pairwise superimpositions of monomeric units of the murine and human TLR4/MD-2 or MD-2 crystal structures in complex with lipid IVa or LPS/lipid A in are shown in Figure 2.
| PDB; complex with ligand L1 |
PDB; complex with ligand L2 |
L1 vs L2: Positions: above / below or equal; Effect 1: Effect 2 |
L1 vs L2: Orientations: fit= backbone positioning as LPS in 3FXI [8] |
|---|---|---|---|
| 3VQ1; dimer: | 3VQ2; dimer: | L4a__LPS; | fit__fit |
| m(TLR4/MD-2/L4a)2 | m(TLR4/MD-2/LPS)2 | AG: AG | |
| 3VQ1; dimer: | 2E59; monomer: | L4a / L4a; | fit / flipped |
| m(TLR4/MD-2/L4a)2 | h(MD-2 /L4a) | AG: AN | |
| 3FXi; dimer: | 2E59; monomer: | LPS / L4a; | fit / flipped |
| h(TLR4 /MD-2 /Ra-LPS)2 | h(MD-2 L4a) | AG: AN | |
| 3FXi; dimer: | 3VQ2; dimer: | LPS__LPS; | fit__fit |
| h(TLR4 /MD-2 /Ra-LPS)2 | m(TLR4/MD-2/LPS)2 | AG: AG |