1wwl
From Proteopedia
Crystal structure of CD14
Structural highlights
Function[CD14_MOUSE] Cooperates with MD-2 and TLR4 to mediate the innate immune response to bacterial lipopolysaccharide (LPS). Acts via MyD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Up-regulates cell surface molecules, including adhesion molecules (By similarity). Evolutionary ConservationCheck, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedLipopolysaccharide, the endotoxin of Gram-negative bacteria, induces extensive immune responses that can lead to fatal septic shock syndrome. The core receptors recognizing lipopolysaccharide are CD14, TLR4, and MD-2. CD14 binds to lipopolysaccharide and presents it to the TLR4/MD-2 complex, which initiates intracellular signaling. In addition to lipopolysaccharide, CD14 is capable of recognizing a few other microbial and cellular products. Here, we present the first crystal structure of CD14 to 2.5 angstroms resolution. A large hydrophobic pocket was found on the NH2-terminal side of the horseshoe-like structure. Previously identified regions involved in lipopolysaccharide binding map to the rim and bottom of the pocket indicating that the pocket is the main component of the lipopolysaccharide-binding site. Mutations that interfere with lipopolysaccharide signaling but not with lipopolysaccharide binding are also clustered in a separate area near the pocket. Ligand diversity of CD14 could be explained by the generous size of the pocket, the considerable flexibility of the rim of the pocket, and the multiplicity of grooves available for ligand binding. Crystal structure of CD14 and its implications for lipopolysaccharide signaling.,Kim JI, Lee CJ, Jin MS, Lee CH, Paik SG, Lee H, Lee JO J Biol Chem. 2005 Mar 25;280(12):11347-51. Epub 2005 Jan 10. PMID:15644310[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
Categories: Large Structures | Lk3 transgenic mice | Jin, M S | Kim, J I | Lee, C H | Lee, C J | Lee, H | Lee, J O | Paik, S G | Cd14 | Immune system | Lp