title: High affinity interleukin-6 receptor is a hexameric complex consisting of two molecules each of interleukin-6, interleukin-6 receptor, and gp-130.
abstract: The high affinity human interleukin-6 (IL-6) receptor complex consists of IL-6 and two membrane-associated receptor components, the IL-6 receptor (alpha-subunit) and the high affinity converter and signal transducing molecule, gp-130 (beta-subunit). Recombinant IL-6 and the extracellular ("soluble") components of the IL-6 receptor (sIL-6R) and gp-130 (sgp-130) have been prepared in order to investigate the stoichiometry and binding of these components in the low affinity (IL-6.sIL-6R) and high affinity (IL-6.sIL-6R.sgp-130) IL-6 receptor complexes. Using a combination of size-exclusion chromatography and analytical ultracentrifugation analysis, in the low affinity receptor complex, IL-6 was shown to bind sIL-6R in a stoichiometric ratio of 1:1, whereas the high affinity ternary complex is hexameric consisting of two molecules each of IL-6, sIL-6R, and sgp-130. This is the first direct demonstration of a higher order arrangement for receptor cytokine interactions that exhibit both high and low affinity complexes.
authors.affiliation: Joint Protein Structure Laboratory, Ludwig Institute for Cancer Research (Melbourne), Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.
authors.forename: L D
authors.initials: LD
authors.lastname: Ward
authors.forename: G J
authors.initials: GJ
authors.lastname: Howlett
authors.forename: G
authors.initials: G
authors.lastname: Discolo
authors.forename: K
authors.initials: K
authors.lastname: Yasukawa
authors.forename: A
authors.initials: A
authors.lastname: Hammacher
authors.forename: R L
authors.initials: RL
authors.lastname: Moritz
authors.forename: R J
authors.initials: RJ
authors.lastname: Simpson
mesh_terms: D000595:Amino Acid Sequence; D015703:Antigens, CD; D002850:Chromatography, Gel; D050822:Cytokine Receptor gp130; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D015850:Interleukin-6 / Q000737:chemistry*; D008562:Membrane Glycoproteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D018123:Receptors, Interleukin / Q000737:chemistry*; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins / Q000737:chemistry; D015398:Signal Transduction; D014461:Ultracentrifugation
chemical_list: D015703:Antigens, CD; C494199:IL6ST protein, human; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D050822:Cytokine Receptor gp130