title: Penta-acylated lipopolisaccharide binds to murine MD-2 but does not induce the oligomerization of TLR4 required for signal transduction.
abstract: A mutant lipopolysaccharide (LPS) lacking a myristate chain in lipid A was shown to be non-pathogenic both in humans and mice. The mutant penta-acylated LPS from the lpxM-strain did not induce TNF-alpha production in murine peritoneal macrophages, or activation of NF-kappaB in transfected cells expressing murine TLR4/MD-2. We prepared a recombinant murine MD-2 in Escherichia coli (E. coli), and examined the binding function. Unexpectedly, specific binding was detected to both wild type and mutant LPS. However, the mutant LPS did not induce conformation changes or oligomerization of TLR4, which have been shown to be required for signal transduction. Mutant LPS appears to fail to induce appropriate conformational changes, resulting in oligomerization of the murine complex for triggering cell responses.
authors.affiliation: Department of Immunology, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Tsuneyoshi
authors.forename: Jun
authors.initials: J
authors.lastname: Kohara
authors.forename: Uleng
authors.initials: U
authors.lastname: Bahrun
authors.forename: Shin-ichiroh
authors.initials: S
authors.lastname: Saitoh
authors.forename: Sachiko
authors.initials: S
authors.lastname: Akashi
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Gauchat
authors.forename: Masao
authors.initials: M
authors.lastname: Kimoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Fukudome
mesh_terms: D000818:Animals; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D047468:Immunoprecipitation; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D051218:Lymphocyte Antigen 96 / Q000378:metabolism*; D051379:Mice; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection
chemical_list: D008070:Lipopolysaccharides; C411728:Ly96 protein, mouse; D051218:Lymphocyte Antigen 96; D011994:Recombinant Proteins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4