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Science 300 (5628): 2101-2104

Copyright © 2003 by the American Association for the Advancement of Science

Hexameric Structure and Assembly of the Interleukin-6/IL-6 {alpha}-Receptor/gp130 Complex

Martin J. Boulanger, Dar-chone Chow,* Elena E. Brevnova,{dagger} K. Christopher Garcia{ddagger}

Abstract: Interleukin-6 (IL-6) is an immunoregulatory cytokine that activates a cell-surface signaling assembly composed of IL-6, the IL-6 {alpha}-receptor (IL-6R{alpha}), and the shared signaling receptor gp130. The 3.65 angstrom–resolution structure of the extracellular signaling complex reveals a hexameric, interlocking assembly mediated by a total of 10symmetry-related, thermodynamically coupled interfaces. Assembly of the hexameric complex occurs sequentially: IL-6 is first engaged by IL-6R{alpha} and then presented to gp130in the proper geometry to facilitate a cooperative transition into the high-affinity, signaling-competent hexamer. The quaternary structures of other IL-6/IL-12 family signaling complexes are likely constructed by means of a similar topological blueprint.

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

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* Present address: Department of Chemistry, University of Houston, 229 Fleming Building, Houston, TX 77204, USA.

{dagger} Present address: Department of Medicine, University of California, San Diego, School of Medicine, 200 West Arbor Drive, San Diego, CA 92103–8382, USA.

{ddagger} To whom correspondence should be addressed. E-mail: kcgarcia{at}stanford.edu

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