Atomic structure of the GCSF-receptor complex showing a new cytokine-receptor recognition scheme.
Granulocyte colony-stimulating factor (GCSF) is the principal growth factor regulating the maturation, proliferation and differentiation of the precursor cells of neutrophilic granulocytes and is used to treat neutropenia. GCSF is a member of the long-chain subtype of the class 1 cytokine superfamily, which includes growth hormone, erythropoietin, interleukin 6 and oncostatin M. Here we have determined the crystal structure of GCSF complexed to the BN-BC domains, the principal ligand-binding region of the GCSF receptor (GCSFR). The two receptor domains form a complex in a 2:2 ratio with the ligand, with a non-crystallographic pseudo-twofold axis through primarily the interdomain region and secondarily the BC domain. This structural view of a gp130-type receptor-ligand complex presents a new molecular basis for cytokine-receptor recognition.
Aritomi
M
M
Biomolecular Engineering Research Institute, Suita-city, Osaka, Japan.
Kunishima
N
N
Okamoto
T
T
Kuroki
R
R
Ota
Y
Y
Morikawa
K
K
D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D016179:Granulocyte Colony-Stimulating Factor / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor