title: Purified monomeric ligand.MD-2 complexes reveal molecular and structural requirements for activation and antagonism of TLR4 by Gram-negative bacterial endotoxins.
abstract: A major focus of work in our laboratory concerns the molecular mechanisms and structural bases of Gram-negative bacterial endotoxin recognition by host (e.g., human) endotoxin-recognition proteins that mediate and/or regulate activation of Toll-like receptor (TLR) 4. Here, we review studies of wild-type and variant monomeric endotoxin.MD-2 complexes first produced and characterized in our laboratories. These purified complexes have provided unique experimental reagents, revealing both quantitative and qualitative determinants of TLR4 activation and antagonism. This review is dedicated to the memory of Dr. Theresa L. Gioannini (1949-2014) who played a central role in many of the studies and discoveries that are reviewed.
authors.affiliation: The Inflammation Program, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, 2501 Crosspark Rd, Coralville, IA, 52241, USA.
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Gioannini
authors.forename: Athmane
authors.initials: A
authors.lastname: Teghanemt
authors.forename: DeSheng
authors.initials: D
authors.lastname: Zhang
authors.forename: Gregory
authors.initials: G
authors.lastname: Esparza
authors.forename: Liping
authors.initials: L
authors.lastname: Yu
authors.forename: Jerrold
authors.initials: J
authors.lastname: Weiss
mesh_terms: D000818:Animals; D004731:Endotoxins / Q000737:chemistry* / Q000276:immunology; D006090:Gram-Negative Bacteria / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D051218:Lymphocyte Antigen 96 / Q000737:chemistry* / Q000276:immunology / Q000302:isolation & purification; D011173:Portraits as Topic; D020836:Protein Structure, Quaternary; D013329:Structure-Activity Relationship; D051197:Toll-Like Receptor 4 / Q000737:chemistry* / Q000276:immunology / Q000302:isolation & purification
chemical_list: D004731:Endotoxins; C495377:LY96 protein, human; D051218:Lymphocyte Antigen 96; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4