A Novel Class of Small Molecule Agonists with Preference for Human over Mouse TLR4 Activation
Fig 12
Change of conformation in a flexible loop region between residues 120 and 129 of human MD-2 upon binding to LPS ligand and dimerization with a second TLR4/MD-2 unit.
Bound and unbound PDB structures were superimposed. The loop region is shown as stick representation (cyan–unbound; yellow–bound), with key residues colored separately (blue–unbound Phe126; magenta–bound Phe126; red–bound Tyr131; green–bound 130 and 132 residues). Bound Phe126 and Tyr131 are additionally rendered with semi-transparent spheres. The rest of MD-2 is shown as backbone trace and only for the unbound structure (cyan). Solid spheres show LPS ligand (orange), TLR4 of the first unit (chain A, green) and TLR4 of the second unit (grey). A) zoom out view with the entire LPS ligand; B) zoom in view with the second TLR4 unit hidden in order to provide better visibility for the conformation of the flexible loop of MD-2.