Structure of the extracellular domains of the human interleukin-6 receptor alpha-chain

Author(s): Varghese, JN; Moritz, RL; Lou, MZ; van Donkelaar, A; Ji, H; Ivancic, N; Branson, KM; Hall, NE; Simpson, RJ;
Details: Publication Year 2002-12-10,Volume 99,Issue #25,Page 15959-15964
Journal Title: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Publication Type: Journal Article
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 (2.4Angstrom) of the IL-61R 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.
Publisher: NATL ACAD SCIENCES
Keywords: HUMAN IL-6 RECEPTOR; N-GLYCOSYLATION SITES; PROTEIN INTERFACES; SHAPE COMPLEMENTARITY; SIGNAL TRANSDUCTION; GP130; COMPLEX; EXPRESSION; MECHANISM; BINDING
Publisher's Version: https://doi.org/10.1073/pnas.232432399
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2002-12-10 12:00:00