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Homodimeric cross-over structure of the human granulocyte colony-stimulating factor (GCSF) receptor signaling complex.

Tamada T., Honjo E., Maeda Y., Okamoto T., Ishibashi M., Tokunaga M., Kuroki R.

A crystal structure of the signaling complex between human granulocyte colony-stimulating factor (GCSF) and a ligand binding region of GCSF receptor (GCSF-R), has been determined to 2.8 A resolution. The GCSF:GCSF-R complex formed a 2:2 stoichiometry by means of a cross-over interaction between the Ig-like domains of GCSF-R and GCSF. The conformation of the complex is quite different from that between human GCSF and the cytokine receptor homologous domain of mouse GCSF-R, but similar to that of the IL-6/gp130 signaling complex. The Ig-like domain cross-over structure necessary for GCSF-R activation is consistent with previously reported thermodynamic and mutational analyses.

Proc. Natl. Acad. Sci. U.S.A. 103:3135-3140(2006) [PubMed] [Europe PMC]

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