Journal
SCIENCE
Volume 300, Issue 5628, Pages 2101-2104Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1083901
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- NIAID NIH HHS [AI51321] Funding Source: Medline
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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-6Ralpha), 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 10 symmetry-related, thermodynamically coupled interfaces. Assembly of the hexameric complex occurs sequentially: IL-6 is. rst engaged by IL-6Ralpha and then presented to gp130 in 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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