LPS:CD14 TLR4:MD2 TLR4:MD2:LPS:CD14 Transfer of LPS onto TLR4 Authored: de Bono, B, 2005-08-16 10:54:15 Edited: Shamovsky, V, 2011-08-12 Pubmed15276183 Pubmed17803912 Pubmed19252480 Pubmed9665271 Reactome Database ID Release 43166041 Reactome, http://www.reactome.org ReactomeREACT_6795 Reviewed: Gay, NJ, 2006-04-24 16:48:17 Reviewed: Gillespie, ME, 2010-11-30 Reviewed: Granucci, Francesca, Zanoni, Ivan, 2012-11-13 The Toll-like receptor 4 (TLR4) is a membrane-spanning protein distantly related to the IL1 receptor. Both CD14 and members of the Toll family contain multiple leucine-rich repeats. In addition, the latter possess a Toll-homology domain in the cytoplasmic tail, which is important in the generation of a transmembrane signal linked to LPS-induced cell activation. Of all Toll family members, TLR4 is probably the exclusive receptor for LPS from most Gram negative organisms.<p> Toll-like receptor 4 and myeloid differentiation factor 2 (MD-2) form a heterodimer that specifically recognizes structurally diverse LPS molecules. A structural study of TLR4:MD-2 complex revealed that MD-2 interaction with TLR4 relies on hydrogen and electrostatic bonds (Kim HM et al, 2007). LPS binds to the hydrophobic pocket of MD-2 and directly mediates the dimerization of the two TLR4:MD-2 complexes in a symmetrical manner. Both hydrophobic and hydrophilic interactions contribute to the main dimerization interaction between MD-2, LPS and TLR4 multimer components. The phosphate groups of LPS also contribute to the receptor multimerization by forming ionic interactions with positively charged residues of TLR4 and MD-2. (Park BS et al, 2009). </p><p>The activated TLR4 receptor is composed of two copies of the TLR4-MD2-LPS complex and initiates signal transduction by recruiting intracellular adaptor molecules. has a Stoichiometric coefficient of 2