Fig. 1

The structure of CD180 compared to TLR4. The extracellular domain of CD180/MD-1 contains leucine rich repeats (LRR) and dimerizes at the C-terminus, thus forming a head-to-head topology (A), which contrasts TLR4/MD-2 that dimerizes at the N-terminus (B). CD180/MD-1 complex forms a 2:2 heterodimer, perhaps in the presence of a lipid molecule (L), which acts as a ligand and binds to the hydrophobic cavity of MD-1. This is analogous to TLR4/MD-2 which binds to lipopolysaccharide (LPS) via a lipid-binding cavity found within MD-2. Whilst CD180 has a small intracellular portion, the intracellular portion of TLR4/MD-2 contains a toll-like/interleukin-1 receptor (TIR) box domain which enables the initiation of intracellular signaling via two alternative pathways: myeloid differentiation primary-response protein 88 (MyD88)-dependent and MyD88-independent