Tamada Taro, Honjo Eijiro, Maeda Yoshitake, Okamoto Tomoyuki, Ishibashi Matsujiro, Tokunaga Masao, Kuroki Ryota
Research Group for Molecular Structural Biology, Quantum Beam Science Directorate, Japan Atomic Energy Agency, Tokai, Ibaraki.
Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3135-40. doi: 10.1073/pnas.0511264103. Epub 2006 Feb 21.
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.
人类粒细胞集落刺激因子(GCSF)与GCSF受体(GCSF-R)的配体结合区域之间信号复合物的晶体结构已确定至2.8埃分辨率。GCSF:GCSF-R复合物通过GCSF-R和GCSF的免疫球蛋白样结构域之间的交叉相互作用形成2:2化学计量比。该复合物的构象与人类GCSF和小鼠GCSF-R的细胞因子受体同源结构域之间的构象有很大不同,但与IL-6/gp130信号复合物的构象相似。GCSF-R激活所需的免疫球蛋白样结构域交叉结构与先前报道的热力学和突变分析一致。