Encyclopedia of Cancer

Living Edition
| Editors: Manfred Schwab


  • Jing Xue
Living reference work entry
DOI: https://doi.org/10.1007/978-3-642-27841-9_5836-9


Toll-like receptor 4 is a protein that in humans is encoded by the TLR4 gene. TLR 4 is the first discovered human toll-like receptor. It recognizes endotoxin (i.e., lipopolysaccharide), an outer membrane component of gram-negative bacteria, that is composed of a conserved amphipathic lipid A component and of variable polysaccharides. The mechanism of TLR4 activation is quite complex and (unlike other TLRs) involves several auxiliary proteins (LBP, CD14) as well as a coreceptor (MD-2). It is in fact MD-2 and not TLR4 that directly recognizes and binds endotoxin. MD-2 is a soluble protein with a large hydrophobic pocket that represents the binding site for the acyl chains of lipid A. Lipid A is usually composed of six acyl chains, but only five of them bind into the hydrophobic pocket of MD-2. The sixth acyl chain protrudes out of the pocket and interacts with hydrophobic residues on TLR4. These interactions are crucial for MD-2/TLR4 heterodimerization and therefore...


TLR4 Expression TLR4 Ligand TLR4 Activation Gastric Cancer Risk Endogenous TLR4 Ligand 
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© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Stanford University School of MedicineStanfordUSA