Hexameric Structure and Assembly of the Interleukin-6/IL-6 α-Receptor/gp130 Complex

lnterleukin-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, interlocki...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2003-06, Vol.300 (5628), p.2101-2104
Main Authors: Boulanger, Martin J., Chow, Dar-Chone, Brevnova, Elena E., Garcia, K. Christopher
Format: Article
Language:English
Subjects:
Antigens, CD - chemistry
Antigens, CD - metabolism
Binding Sites
Biological and medical sciences
Cellular biology
Crystal structure
Crystalline structure
Crystallography, X-Ray
Cytokine Receptor gp130
Cytokines
Electron density
Epitopes
Fundamental and applied biological sciences. Psychology
Humans
Immunology
Interleukin-6 - chemistry
Interleukin-6 - metabolism
Macromolecular Substances
Membrane Glycoproteins - chemistry
Membrane Glycoproteins - metabolism
Models, Molecular
Molecular biophysics
Molecules
Protein Binding
Protein Conformation
Protein Structure, Secondary
Protein Structure, Tertiary
Receptors
Receptors, Interleukin-6 - chemistry
Receptors, Interleukin-6 - metabolism
Signal reflection
Signal Transduction
Structure in molecular biology
Surface areas
Symmetry
Thermodynamics
Titration
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Description
Summary:lnterleukin-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 10 symmetry-related, thermodynamically coupled interfaces. Assembly of the hexameric complex occurs sequentially: IL-6 is first engaged by IL-6Rα 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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1083901