Structure of the extracellular domains of the human interleukin-6 receptor alpha -chain.
Dysregulated production of IL-6 and its receptor (IL-6R) are implicated in the pathogenesis of multiple myeloma, autoimmune diseases and prostate cancer. The IL-6R complex comprises two molecules each of IL-6, IL-6R, and the signaling molecule, gp130. Here, we report the x-ray structure (2.4 A) of the IL-6R ectodomains. The N-terminal strand of the Ig-like domain (D(1)) is disulfide-bonded to domain D(2), and domains D(2) and D(3), the cytokine-binding domain, are structurally similar to known cytokine-binding domains. The head-to-tail packing of two closely associated IL-6R molecules observed in the crystal may be representative of the configuration of the physiological dimer of IL-6R and provides new insight into the architecture of the IL-6R complex.
Varghese
J N
JN
Biomolecular Research Institute and Commonwealth Scientific and Industrial Research Organization Health Sciences and Nutrition, 343 Royal Parade, Parkville 3052, Australia.
Moritz
R L
RL
Lou
M-Z
MZ
Van Donkelaar
A
A
Ji
H
H
Ivancic
N
N
Branson
K M
KM
Hall
N E
NE
Simpson
R J
RJ
D020816:Amino Acid Motifs; D001665:Binding Sites; D001704:Biopolymers; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D046911:Macromolecular Substances; D008958:Models, Molecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D019947:Receptors, Interleukin-6 / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction
D001704:Biopolymers; D015850:Interleukin-6; D046911:Macromolecular Substances; D019947:Receptors, Interleukin-6