%0 Journal Article
%T Three-dimensional structure and function study on the active region in the extracellular ligand-binding domain of human IL-6 receptor
%A REN Yunfang FENG Jiannan
%A QU Hong
%A LI Song
%A SHEN Beifen
%A <br>任蕴芳
%A 冯健男
%A 曲红
%A 李松
%A 沈倍奋
%J 中国科学C辑(英文版)
%D 2000
%I Springer
%X In this study the three-dimensional (3-D) model of the ligand-binding domain (V106-P322) of human interleukin-6 receptor (hlL-6 R) was constructed by computer-guided ho-mology modeling technique using the crystal structure of the ligand-binding domain (K52-L251) of human growth hormone receptor (hGHR) as templet. Furthermore, the active binding region of the 3-D model of hlL-6R with the ligand (hlL-6) was predicted. In light of the structural characteristics of the active region, a hydrophobic pocket shielded by two hydrophilic residues (E115 and E505) of the region was identified by a combination of molecular modelling and the site-directed or double-site mutation of the twelve crucial residues in the ligand-binding domain of hIL-6R (V106-P322). We observed and analyzed the effects of these mutants on the spatial conformation of the pocket-like region of hlL-6 R. The results indicated that any site-directed mutation of the five Cys residues (four conservative Cys residues: Cyst 21, Cys132, Cys165, Cys176; near membrane Cys residue: Cys193) or each double-site mutation of the five residues in WSEWS motif of hIL-6R (V106-P322) makes the corresponding spatial conformation of the pocket region block the linkage between hlL-6 R and hlL-6. However, the influence of the site-directed mutation of Cys211 and Cys277 individually on the conformation of the pocket region benefits the interaction between hlL-6R and hlL-6. Our study suggests that the predicted hydrophobic pocket in the 3-D model of hIL-6R (V106-P322) is the critical molecular basis for the binding of hlL-6R with its ligand, and the active pocket may be used as a target for designing small hlL-6R-inhibiting molecules in our further study.
%K human interleukin-6 receptor
%K ligand-binding domain
%K active region
%K 3-D structure and function<br>
%U http://www.alljournals.cn/get_abstract_url.aspx?pcid=90BA3D13E7F3BC869AC96FB3DA594E3FE34FBF7B8BC0E591&jid=180CF3A72E750F3261A8A60EDC957784&aid=12A92AD57243489ECB7BDD48FF6DABEB&yid=9806D0D4EAA9BED3&vid=BE33CC7147FEFCA4&iid=E158A972A605785F&sid=F10601728A1E9BEA&eid=4BEA9A781F286FC6&journal_id=1674-7305&journal_name=ScienceChina.Lifesciences&referenced_num=1&reference_num=15