Recognition of Lipopolysaccharides byTLR4 and its Accessory Proteins

Abstract

Lipopolysaccharide (LPS) is a bacterial glycolipid that is the major component of the outer membrane of gram-negative bacteria. It serves as an early warning signal of infection by initiating a potent immune response. Lipid A, the lipid part of the LPS, is responsible for the majority of the immunological activity of LPS and binds to the cell surface receptor, TLR4-MD-2 heterodimer. LPS binds to the hydrophobic pocket in MD-2 and induces the dimerization of TLR4. Efficient activation the TLR4 signal in vivo requires accessory proteins, LBP and CD14. LBP is a serum glycoprotein that can extract LPS from bacterial membranes or vesicles released from it. CD14 accepts a monomeric form of LPS from LBP and delivers it to the TLR4-MD-2 complex. The structures of these LPS recognition proteins in a complex with LPS and related molecules provide us insight into how our immune system recognizes bacterial infections and initiates efficient defense mechanisms. In this review, we will summarize recent structural studies of these LPS receptors and accessory proteins.