title: Structure of the extracellular domains of the human interleukin-6 receptor alpha -chain.
abstract: Dysregulated production of IL-6 and its receptor (IL-6R) are implicated in the pathogenesis of multiple myeloma, autoimmune diseases and prostate cancer. The IL-6R complex comprises two molecules each of IL-6, IL-6R, and the signaling molecule, gp130. Here, we report the x-ray structure (2.4 A) of the IL-6R ectodomains. The N-terminal strand of the Ig-like domain (D(1)) is disulfide-bonded to domain D(2), and domains D(2) and D(3), the cytokine-binding domain, are structurally similar to known cytokine-binding domains. The head-to-tail packing of two closely associated IL-6R molecules observed in the crystal may be representative of the configuration of the physiological dimer of IL-6R and provides new insight into the architecture of the IL-6R complex.
authors.affiliation: Biomolecular Research Institute and Commonwealth Scientific and Industrial Research Organization Health Sciences and Nutrition, 343 Royal Parade, Parkville 3052, Australia.
authors.forename: J N
authors.initials: JN
authors.lastname: Varghese
authors.forename: R L
authors.initials: RL
authors.lastname: Moritz
authors.forename: M-Z
authors.initials: MZ
authors.lastname: Lou
authors.forename: A
authors.initials: A
authors.lastname: Van Donkelaar
authors.forename: H
authors.initials: H
authors.lastname: Ji
authors.forename: N
authors.initials: N
authors.lastname: Ivancic
authors.forename: K M
authors.initials: KM
authors.lastname: Branson
authors.forename: N E
authors.initials: NE
authors.lastname: Hall
authors.forename: R J
authors.initials: RJ
authors.lastname: Simpson
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D001704:Biopolymers; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D046911:Macromolecular Substances; D008958:Models, Molecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D019947:Receptors, Interleukin-6 / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001704:Biopolymers; D015850:Interleukin-6; D046911:Macromolecular Substances; D019947:Receptors, Interleukin-6