title: MD-2.
abstract: Toll-like receptors (TLRs) are a small family of type-I glycoproteins that bind to and are activated by conserved non-self molecular signatures carried by microorganisms. Toll-like receptor 4 is triggered by most lipopolysaccharides (LPS). LPS is a complex amphipathic saccharolipidic glycan derived from Gram-negative bacteria. Unique among TLRs, TLR4 activity and interaction with its natural ligand(s) strictly depends on the presence of the extracellular adaptor MD-2. MD-2 is a small secreted glycoprotein that binds with cytokine-like affinities to both the hydrophobic portion of LPS and to the extracellular domain of TLR4. The interaction between MD-2 and LPS induces a triggering event on TLR4, which involves the molecular rearrangement of the receptor complex and its homotypic aggregation. In silico analysis suggests that MD-2 and MD-1 are paralogs derived from a common predecessor at the level of early vertebrates. In this review, we summarize the current state of knowledge concerning MD-2.
authors.affiliation: Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA. alberto.visintin@umassmed.edu
authors.forename: Alberto
authors.initials: A
authors.lastname: Visintin
authors.forename: Dimitar B
authors.initials: DB
authors.lastname: Iliev
authors.forename: Brian G
authors.initials: BG
authors.lastname: Monks
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Halmen
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Golenbock
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001419:Bacteria / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D007249:Inflammation / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D051218:Lymphocyte Antigen 96 / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D051197:Toll-Like Receptor 4 / Q000502:physiology
chemical_list: D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; D051197:Toll-Like Receptor 4