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Fig. 1. Lipopolysaccharide transfer cascade to the TLR4/MD2 complex via LBP and CD14. (A) Crystal structure of LBP (PDB: 4M4D), CD14 (PDB: 1WWL), TLR4/MD2 complex (PDB: 2Z64), and TLR4/MD2/LPS complex (PDB: 3FXI). (B) 2D class average of LPS micelle-bound LBP (top left), a representative negative-stained TEM image of LPS micelle/LBP/CD14 (top right, sky-blue arrow: LPS micelle-bound LBP, green arrow: CD14), and schematic model of sequential LPS transport to the TLR4/MD2 complex (bottom). N-terminal tip of LBP binds to LPS micelle and the concave surface in the C-terminal domain of CD14 interacts with C-terminal tip of LBP to obtain a single LPS molecule. The LPS-bound CD14 is rapidly dissociated from the LBP by electrostatic repulsion and another CD14 binds to the LBP. CD14/LPS interacts with LRR13–15 domains of TLR4 to transfer LPS to TLR4/MD2. Two LPS-bound TLR4/MD2 complexes form a M-shaped dimer, followed by activation of the signaling pathway for the innate immune response.
BMB Reports 2017;50:55~57
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