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.