UC San Diego
Molecular Basis of Interaction between Toll-like Receptor 4 and Apolipoprotein A-I Binding Protein
- Author(s): Xia, Yining
- Advisor(s): Miller, Yury
- et al.
Inflammation is a response of immune cells to microbial pathogen-associated and host damage-associated molecular patterns. Toll-like receptor 4 (TLR4) is a major immune, pattern-recognition receptor that recognizes these ligands and initiates inflammatory signaling. Previous studies have shown that binding of Apolipoprotein A-I binding protein (AIBP) to TLR4 facilitates removal of excess cholesterol from endothelial cells and macrophages, resulting in the reduction of membrane lipid rafts and inhibition of TLR4 dimerization and reduced inflammatory responses. However, the molecular basis of interaction between TLR4 and AIBP is not fully understood. Here, I investigate TLR4 binding motifs in the AIBP molecule. Using wildtype AIBP and mutated variants of AIBP expressed and purified from a baculovirus/insect cell system, I identified a TLR4 binding domain in the AIBP molecule, which plays a critical role in regulation of TLR4-dependent inflammatory responses in microglia. My findings provide important mechanistic insights into the molecular basis of interaction between TLR4 and AIBP and may contribute to the development of AIBP-based therapy for chronic inflammatory diseases, including atherosclerosis and neuropathic pain.