Hexameric Structure and Assembly of the Interleukin-6/IL-6 α-Receptor/gp130 Complex
Abstract
Interleukin-6 (IL-6) is an immunoregulatory cytokine that activates a cell-surface signaling assembly composed of IL-6, the IL-6 α-receptor (IL-6Rα), 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-6Rα 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.
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We gratefully acknowledge assistance and helpful discussions with G. McDermott, N. Goriatcheva, M. Martick, F. Bazan, S. Rose-John, J. Heath, and Y. Jones. We also acknowledge Stanford Synchrotron Radiation Laboratory and Advanced Light Source for x-ray resources. This study was supported by the NIH (AI51321), Cancer Research Institute, University of California–Davis Cancer Research Program, Pew Charitable Trusts, and American Heart Association. M.J.B. is supported by a National Sciences and Engineering Research Council of Canada postdoctoral fellowship. Coordinates of the asymmetric unit have been deposited in the Protein Data Bank with accession code 1P9M (RCSB019180). The complete biological hexameric assembly is also available from the authors.
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Science
Volume 300 | Issue 5628
27 June 2003
27 June 2003
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American Association for the Advancement of Science.
Submission history
Received: 26 February 2003
Accepted: 23 May 2003
Published in print: 27 June 2003
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