Details of Toll-like receptor : adapter interaction revealed by germ-line mutagenesis

Jiang  ZF; Georgel  P; Li  CLChoe  JCrozat  KRutschmann  SDu  XBigby  TMudd  SSovath  S

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Details of Toll-like receptor : adapter interaction revealed by germ-line mutagenesis

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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.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2006年第29期|10961-10966|共6页
作者
Jiang ZF; Georgel P; Li CLChoe JCrozat KRutschmann SDu XBigby TMudd SSovath S;
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作者单位

Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA;

Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA;

Vet Adm San Diego Hlth Care Syst, Dept Med, San Diego, CA 92161 USA;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
genetics; MyD88; positional cloning; signaling; NF-KAPPA-B; SIGNALING PATHWAY; TIR DOMAIN; TRANSDUCTION; PROTEINS; MYD88; MOLECULE; PROGRAMS; INNATE; GENE;

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机译：TIR-containing adapter molecule (TICAM)-2, a bridging adapter recruiting to toll-like receptor 4 TICAM-1 that induces interferon-beta.
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Details of Toll-like receptor : adapter interaction revealed by germ-line mutagenesis

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