Abstract: The high affinity interleukin-6 (IL-6) receptor is
a hexameric complex consisting of two molecules each of IL-6, IL-6 receptor
(IL-6R), and the high affinity converter and signaling molecule, gp130.
The extracellular "soluble" part of the IL-6R (sIL-6R) consists of three
domains: an amino-terminal Ig-like domain and two fibronectin-type III
(FN III) domains. The two FN III domains comprise the cytokine-binding
domain defined by a set of 4 conserved cysteine residues and a WSXWS sequence
motif. Here, we have determined the disulfide structure of the human sIL-6R
by peptide mapping in the absence and presence of reducing agent. Mass
spectrometric analysis of these peptides revealed four disulfide bonds
and two free cysteines. The disulfides Cys102-Cys113 and Cys146-Cys157
are consistent with known cytokine-binding domain motifs, and Cys28-Cys77
with known Ig superfamily domains. An unusual cysteine connectivity between
Cys6-Cys174, which links the Ig-like and NH2-terminal FN III domains causing
them to fold back onto each other, has not previously been observed among
cytokine receptors. The two free cysteines (Cys192 and Cys258) were detected
as cysteinyl-cysteines, although a small proportion of Cys258 was reactive
with the alkylating agent 4-vinylpyridine. Of the four potential N-glycosylation
sites, carbohydrate moieties were identified on Asn36, Asn74, and Asn202,
but not on Asn226.
PDB coordinates of the extracellular domain of IL-6R can be downloaded below. Right click on the link below in order to save the link as a file.
PUBMED ID 10066782