人白介素6受体胞外区三维结构的同源模拟

Homology Modeling of the Functional Domain of the Extracellular Region of Human IL-6 Receptor

IL 6受体是造血因子超家族成员 ,其胞外区细胞因子结合结构域 (CBD)是受体结合配基和偶联gp1 30转导IL 6信号的功能域 .据预测 ,IL 6R功能域的β片层折叠模式和人生长激素受体 ( hGH R)及CD4 的晶体结构十分相似 .应用计算机同源模拟技术 ,以hGH R和CD4 的三维结构为模板 ,模建了hIL 6R功能域 ( 1 0 6～ 32 2位 )的三维结构 ,初步描述了其结构保守区的构象特征 .文章研究模建的hIL 6R三维结构模式为探讨可溶性IL 6R点突变的结果 ,以及进行三维定量分析IL 6R胞外区功能域的构效关系提供了空间结构基础 .

Interleukin-6 receptor (IL-6R) is a member of the hematopoietin receptor superfamily which has its common conservative structure “the cytokine binding domain (CBD)”. CBD is the functional domain of the extracellular region of IL-6R, because only this domain of IL-6R is responsible for IL-6-binding and for IL-6 signal transduction through gp130. It is proposed that the β-sheets folding motif of the IL-6R CBD is very similar to that seen in the crystal structure of human growth hormone receptor (hGH-R), which also belongs to the cytokine receptor fam- ily, and CD4. By means of computer-guided homology modeling techniques, the three- dimensional (3D) structures of hGH-R and CD 4 were used as template protein to predict the 3D-structure of the functional domain (residue 106～322) of hIL-6R. The characteristics of the conservative structure-conformation in CBD of hIL-6R were described. The model may provide for the interpretation of the results obtained with introducing site-directed mutation into soluble IL-6R and the 3D-quantitative analysis on the structure-function relationship of IL-6R functional domain.