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Hexameric structure and assembly of the interleukin-6/IL-6 alpha-receptor/gp130 complex

Martin J Boulanger1, Dar-chone Chow, Elena E Brevnova

  • 1Department of Microbiology and Immunology and Department of Structural Biology, Stanford University School of Medicine, Fairchild D319, 299 Campus Drive, Stanford, CA 94305-5124, USA.

Science (New York, N.Y.)
|June 28, 2003
PubMed

Insights

This study reveals the hexameric structure of the Interleukin-6 (IL-6) signaling complex, detailing how IL-6 engages its receptors. Understanding this assembly is key to cytokine signaling mechanisms.

Area of Science:

  • Immunology
  • Structural Biology
  • Molecular Biology

Background:

  • Interleukin-6 (IL-6) is a critical immunoregulatory cytokine.
  • IL-6 signaling involves IL-6, IL-6 receptor alpha (IL-6Ralpha), and gp130.
  • Understanding the structural basis of IL-6 complex assembly is crucial for deciphering its biological functions.

Purpose of the Study:

  • To determine the high-resolution structure of the extracellular IL-6 signaling complex.
  • To elucidate the sequential assembly mechanism of the IL-6/IL-6Ralpha/gp130 hexamer.
  • To provide insights into the structural blueprint of related cytokine signaling complexes.

Main Methods:

  • X-ray crystallography was used to determine the structure.
  • The resolution of the determined structure was 3.65 angstroms.
  • Analysis of symmetry-related interfaces and thermodynamic coupling was performed.

Main Results:

  • The extracellular signaling complex forms a hexameric, interlocking assembly.
  • Ten symmetry-related, thermodynamically coupled interfaces mediate the complex assembly.
  • Sequential engagement of IL-6 by IL-6Ralpha, followed by gp130, facilitates hexamer formation.

Conclusions:

  • The IL-6 signaling complex adopts a specific hexameric quaternary structure.
  • A sequential binding mechanism drives the formation of the signaling-competent hexamer.
  • This structural blueprint may be conserved across other IL-6/IL-12 family signaling complexes.

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