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

Homodimeric cross-over structure of the human granulocyte colony-stimulating factor (GCSF) receptor signaling complex
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DOI:
10.1073/pnas.0511264103
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发表时间:
2006-02-28
影响因子:
11.1
通讯作者:
Kuroki, R
Kuroki, R
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Tamada, T;Honjo, E;Kuroki, R

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人粒细胞集落刺激因子(GCSF)和GCSF受体(GCSF-R)的配体结合区之间的信号传导复合物的晶体结构已被确定为2.8埃分辨率。GCSF:GCSF-R复合物通过GCSF-R和GCSF的Ig样结构域之间的交叉相互作用形成2:2的化学计量比。该复合物的构象与人GCSF和小鼠GCSF-R的细胞因子受体同源结构域之间的构象完全不同,但与IL-6/gp 130信号传导复合物的构象相似。GCSF-R激活所需的Ig样结构域交叉结构与先前报道的热力学和突变分析一致。
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 angstrom 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 lL-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.