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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.

SUBMITTER: Varghese JN

PROVIDER: S-EPMC138547 | biostudies-literature | 2002 Dec

REPOSITORIES: biostudies-literature

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

Varghese J N JN Moritz R L RL Lou M-Z MZ Van Donkelaar A A Ji H H Ivancic N N Branson K M KM Hall N E NE Simpson R J RJ

Proceedings of the National Academy of Sciences of the United States of America 20021202 25

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 c ...[more]

PMID: 12461182

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