Penta-acylated lipopolisaccharide binds to murine MD-2 but does not induce the oligomerization of TLR4 required for signal transduction.
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.
Tsuneyoshi
Naoko
N
Department of Immunology, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan.
Kohara
Jun
J
Bahrun
Uleng
U
Saitoh
Shin-ichiroh
S
Akashi
Sachiko
S
Gauchat
Jean-François
JF
Kimoto
Masao
M
Fukudome
Kenji
K
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
D008070:Lipopolysaccharides; C411728:Ly96 protein, mouse; D051218:Lymphocyte Antigen 96; D011994:Recombinant Proteins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4