High affinity interleukin-6 receptor is a hexameric complex consisting of two molecules each of interleukin-6, interleukin-6 receptor, and gp-130.
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.
Ward
L D
LD
Joint Protein Structure Laboratory, Ludwig Institute for Cancer Research (Melbourne), Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Howlett
G J
GJ
Discolo
G
G
Yasukawa
K
K
Hammacher
A
A
Moritz
R L
RL
Simpson
R J
RJ
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
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