网站地图 加入收藏 中文 English
 
首页 中心概况 组织机构 研究队伍 科学研究 人才培养 交流合作 支撑服务 人才招聘 下载专区 联系我们
当前位置:首页 - 科学研究 - 学术论文
学术论文
Jiang ZF, Georgel P, Li CL, Choe JW, Crozat K, Rutschmann S, Du X, Bigby T, Mudd S, Sovath SY, Wilson IA, Olson A, Beutler B*, Details of Toll-like receptor:adapter interaction revealed by germ-line mutagenesis, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 103(29), 10961-66, 2006.
发布时间:2011-11-23作者:蒋争凡关键字:

Abstract
The immunovariant N-ethyl-N-nitrosourea-induced mutations Pococurante (Poc) and Lackadaisical were found to alter MyD88, creating striking receptor-selective effects. Poc, in particular, prevented sensing of all MyD88-dependent Toll-like receptor (TLR) ligands except diacyl lipopeptides. Furthermore, Poc-site and classical BB loop mutations caused equivalent phenotypes when engrafted into any TLR/IL-1 receptor/resistance (TIR) domain. These observations, complemented by data from docking studies and site-directed mutagenesis, revealed that BB loops and Poc sites interact homotypically across the receptor:adapter signaling interface, whereas the C-terminal alpha(E)-helices support adapter:adapter and receptor:receptor oligomerization. We have thus defined the TIR domain surface that mediates association between TLRs and MyD88 and the surface required for MyD88 or TLR oligomerization. Moreover, MyD88 engages individual TLRs differently, suggesting the feasibility of selective pharmacologic TIR domain receptor blockade.




版权所有 生命科学联合中心 京ICP备15006448号-5