Hexameric structure and assembly of the interleukin-6/IL-6 alpha-receptor/gp130 complex.
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 first engaged by IL-6Ralpha 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.
Boulanger
Martin J
MJ
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.
Chow
Dar-chone
DC
Brevnova
Elena E
EE
Garcia
K Christopher
KC
D015703:Antigens, CD / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D050822:Cytokine Receptor gp130; D006801:Humans; D015850:Interleukin-6 / Q000737:chemistry* / Q000378:metabolism*; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D019947:Receptors, Interleukin-6 / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction; D013816:Thermodynamics
D015703:Antigens, CD; C494199:IL6ST protein, human; D015850:Interleukin-6; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D019947:Receptors, Interleukin-6; C113250:interleukin-6 receptor alpha; D050822:Cytokine Receptor gp130