title: Seeing double: crystal structures of the type I TNF receptor.
abstract: The crystal structure of the extracellular domain of the type I tumor necrosis factor receptor (sTNF-R1) has been determined to 2.25 A at pH 7.5. We have also solved the structure of sTNF-R1 at pH 3.7. sTNF-R1 is an elongated molecule consisting of a linear combination of four cysteine-rich motifs. Interestingly, the crystal structure reveals two distinct dimers of the receptor. One dimer is formed by a parallel arrangement of receptors, the other by an antiparallel arrangement of receptors. In the parallel arrangement of the receptors, the tumor necrosis factor (TNF) binding face of the receptor is completely exposed to solvent. However, in the antiparallel arrangement, the TNF binding face is intimately involved in the dimer interactions. Details of these recognition surfaces are discussed. Both these dimer interactions bury substantial surface area, comprise polar and apolar contact surfaces and have complimentary recognition surfaces. Thus these interactions are typical of genuine protein-protein interactions, rather than crystal packing contacts. These dimers may function to inhibit signal transduction in the absence of TNF or in the case of the parallel dimer, promote clustering of TNF/TNF receptor complexes on the cell surface.
authors.affiliation: Centre for Biomolecular Sciences, University of St. Andrews, Fife, Scotland, UK.
authors.forename: J H
authors.initials: JH
authors.lastname: Naismith
authors.forename: B J
authors.initials: BJ
authors.lastname: Brandhuber
authors.forename: T Q
authors.initials: TQ
authors.lastname: Devine
authors.forename: S R
authors.initials: SR
authors.lastname: Sprang
mesh_terms: D001665:Binding Sites; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D011992:Endosomes / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008233:Lymphotoxin-alpha / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008233:Lymphotoxin-alpha; D018124:Receptors, Tumor Necrosis Factor