Abstract
Bacterial lipopolysaccharides (LPS) typically consist of a hydrophobic domain known as lipid A (or endotoxin), a nonrepeating "core" oligosaccharide, and a distal polysaccharide (or O-antigen). Recent genomic data have facilitated study of LPS assembly in diverse Gram-negative bacteria, many of which are human or plant pathogens, and have established the importance of lateral gene transfer in generating structural diversity of O-antigens. Many enzymes of lipid A biosynthesis like LpxC have been validated as targets for development of new antibiotics. Key genes for lipid A biosynthesis have unexpectedly also been found in higher plants, indicating that eukaryotic lipid A-like molecules may exist. Most significant has been the identification of the plasma membrane protein TLR4 as the lipid A signaling receptor of animal cells. TLR4 belongs to a family of innate immunity receptors that possess a large extracellular domain of leucine-rich repeats, a single trans-membrane segment, and a smaller cytoplasmic signaling region that engages the adaptor protein MyD88. The expanding knowledge of TLR4 specificity and its downstream signaling pathways should provide new opportunities for blocking inflammation associated with infection.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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ATP-Binding Cassette Transporters*
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Animals
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Anti-Bacterial Agents / metabolism
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Bacterial Proteins / chemistry
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism
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Biological Transport / physiology
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Drosophila Proteins*
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Genes, Plant
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Gram-Negative Bacteria / chemistry*
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Gram-Negative Bacteria / genetics
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Gram-Negative Bacteria / metabolism
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Hexosyltransferases / metabolism
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Humans
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Immunity, Innate / immunology
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Immunity, Innate / physiology
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Lipopolysaccharides* / chemistry
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Lipopolysaccharides* / immunology
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Lipopolysaccharides* / metabolism
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism
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Membrane Proteins / chemistry
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Models, Biological
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Molecular Structure
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Oligosaccharides / chemistry
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Oligosaccharides / metabolism
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Protein Structure, Tertiary
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism
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Toll-Like Receptor 4
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Toll-Like Receptors
Substances
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ATP-Binding Cassette Transporters
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Anti-Bacterial Agents
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Bacterial Proteins
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Drosophila Proteins
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Lipopolysaccharides
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Membrane Glycoproteins
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Membrane Proteins
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MsbA protein, Bacteria
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Oligosaccharides
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Receptors, Cell Surface
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TLR4 protein, human
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Toll-Like Receptor 4
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Toll-Like Receptors
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Hexosyltransferases
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O-antigen polymerase