title: A domain in TNF receptors that mediates ligand-independent receptor assembly and signaling.
abstract: A conserved domain in the extracellular region of the 60- and 80-kilodalton tumor necrosis factor receptors (TNFRs) was identified that mediates specific ligand-independent assembly of receptor trimers. This pre-ligand-binding assembly domain (PLAD) is physically distinct from the domain that forms the major contacts with ligand, but is necessary and sufficient for the assembly of TNFR complexes that bind TNF-alpha and mediate signaling. Other members of the TNFR superfamily, including TRAIL receptor 1 and CD40, show similar homotypic association. Thus, TNFRs and related receptors appear to function as preformed complexes rather than as individual receptor subunits that oligomerize after ligand binding.
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: F K
authors.initials: FK
authors.lastname: Chan
authors.forename: H J
authors.initials: HJ
authors.lastname: Chun
authors.forename: L
authors.initials: L
authors.lastname: Zheng
authors.forename: R M
authors.initials: RM
authors.lastname: Siegel
authors.forename: K L
authors.initials: KL
authors.lastname: Bui
authors.forename: M J
authors.initials: MJ
authors.lastname: Lenardo
mesh_terms: D019943:Amino Acid Substitution; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism; D017209:Apoptosis; D001665:Binding Sites; D003432:Cross-Linking Reagents; D019281:Dimerization; D004735:Energy Transfer; D005453:Fluorescence; D006801:Humans; D008024:Ligands; D046911:Macromolecular Substances; D009154:Mutation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry* / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D013388:Succinimides; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D003432:Cross-Linking Reagents; D008024:Ligands; D046911:Macromolecular Substances; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011993:Recombinant Fusion Proteins; D013388:Succinimides; D014409:Tumor Necrosis Factor-alpha; C035759:3,3'-dithiobis(sulfosuccinimidyl propionate)