title: A single amino acid of toll-like receptor 4 that is pivotal for its signal transduction and subcellular localization.
abstract: Toll-like receptor 4 (TLR4) is essential for recognizing a Gram-negative bacterial component, lipopolysaccharide (LPS). A single amino acid mutation at position 712 of murine TLR4 leads to hyporesponsiveness to LPS. In this study we determined that an amino acid, a leucine at position 815 of human TLR4, is also pivotal for LPS responsiveness and subcellular distribution. By replacing the leucine with alanine, the mutant TLR4 lost responsiveness to LPS and did not localize on the plasma membrane. In addition, it does not coprecipitate with myeloid differentiation-2, an accessory protein that is necessary for TLR4 to recognize LPS. These results suggest that the leucine at position 815 is required for the normal maturation of TLR4 and for formation of the TLR4.MD-2 complex.
authors.affiliation: Center for Structuring Life Sciences, Graduate school of Arts and Sciences, University of Tokyo, Tokyo 153-8903, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Yanagimoto
authors.forename: Keita
authors.initials: K
authors.lastname: Tatsuno
authors.forename: Shu
authors.initials: S
authors.lastname: Okugawa
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Kitazawa
authors.forename: Kunihisa
authors.initials: K
authors.lastname: Tsukada
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Koike
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kimura
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Shibasaki
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ota
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism*; D051218:Lymphocyte Antigen 96 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D020125:Mutation, Missense; D011485:Protein Binding / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
chemical_list: C495377:LY96 protein, human; D008070:Lipopolysaccharides; C411728:Ly96 protein, mouse; D051218:Lymphocyte Antigen 96; D046912:Multiprotein Complexes; C495345:TLR4 protein, human; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4