Lipopolysaccharide (LPS) is a major component of the outer membrane of Gram-negative bacteria and is recognized by the innate immune system through a cascade of receptors, including LPS binding protein (LBP), CD14, and the TLR4-MD-2 complex. LPS triggers immune responses that help combat infection, but excessive LPS response can lead to septic shock. The structural basis of LPS recognition by these receptors is crucial for understanding immune responses and developing anti-sepsis drugs. LPS is a complex molecule composed of a hydrophobic lipid A region and a carbohydrate chain. The lipid A portion is responsible for most of LPS's immunological activity. LPS is initially bound by LBP, which transfers it to CD14, which then presents it to the TLR4-MD-2 complex. The TLR4-MD-2 complex is a key receptor for LPS, and its structure has been studied in detail. The TLR4-MD-2 complex has a unique structure that allows it to recognize LPS and initiate signaling pathways leading to the production of pro-inflammatory cytokines. The TLR4-MD-2 complex is composed of TLR4 and MD-2, which form a heterodimer. MD-2 is a small protein that binds to TLR4 and is essential for LPS recognition. The structure of the TLR4-MD-2 complex has been determined, revealing how it binds to LPS and initiates signaling. The binding of LPS to the TLR4-MD-2 complex induces dimerization, which is essential for signaling. The structure of the TLR4-MD-2 complex also provides insights into how LPS activates immune responses. Other TLRs, such as TLR2, TLR6, TLR3, TLR5, TLR7, and TLR8, recognize different microbial molecules, including lipopeptides, double-stranded RNA, flagellin, and single-stranded RNA. The structures of these TLRs and their interactions with ligands have been studied, revealing how they recognize and respond to different pathogens. The TLR family plays a critical role in the innate immune system, and understanding their structures and functions is essential for developing new therapies for infectious diseases and inflammatory conditions.Lipopolysaccharide (LPS) is a major component of the outer membrane of Gram-negative bacteria and is recognized by the innate immune system through a cascade of receptors, including LPS binding protein (LBP), CD14, and the TLR4-MD-2 complex. LPS triggers immune responses that help combat infection, but excessive LPS response can lead to septic shock. The structural basis of LPS recognition by these receptors is crucial for understanding immune responses and developing anti-sepsis drugs. LPS is a complex molecule composed of a hydrophobic lipid A region and a carbohydrate chain. The lipid A portion is responsible for most of LPS's immunological activity. LPS is initially bound by LBP, which transfers it to CD14, which then presents it to the TLR4-MD-2 complex. The TLR4-MD-2 complex is a key receptor for LPS, and its structure has been studied in detail. The TLR4-MD-2 complex has a unique structure that allows it to recognize LPS and initiate signaling pathways leading to the production of pro-inflammatory cytokines. The TLR4-MD-2 complex is composed of TLR4 and MD-2, which form a heterodimer. MD-2 is a small protein that binds to TLR4 and is essential for LPS recognition. The structure of the TLR4-MD-2 complex has been determined, revealing how it binds to LPS and initiates signaling. The binding of LPS to the TLR4-MD-2 complex induces dimerization, which is essential for signaling. The structure of the TLR4-MD-2 complex also provides insights into how LPS activates immune responses. Other TLRs, such as TLR2, TLR6, TLR3, TLR5, TLR7, and TLR8, recognize different microbial molecules, including lipopeptides, double-stranded RNA, flagellin, and single-stranded RNA. The structures of these TLRs and their interactions with ligands have been studied, revealing how they recognize and respond to different pathogens. The TLR family plays a critical role in the innate immune system, and understanding their structures and functions is essential for developing new therapies for infectious diseases and inflammatory conditions.