韓國科學(xué)家日前宣布，他們已經(jīng)破譯了誘發(fā)敗血癥的肌體防御機(jī)制,。
據(jù)韓聯(lián)社報(bào)道，以韓國高等科學(xué)技術(shù)院的化學(xué)家李知昊（音譯）為首的研究小組稱,，他們已繪制出會(huì)導(dǎo)致血中毒的ＴＬＲ１和ＴＬＲ２兩種受體的基因圖,，研究結(jié)果發(fā)表在最新一期的《細(xì)胞》月刊上。
這個(gè)研究小組還于本月稍早時(shí)候公布了一項(xiàng)類似的突破性發(fā)現(xiàn),，他們繪制出了小鼠ＴＬＲ４（ＴＬＲ４－ＭＤ－２）受體的結(jié)構(gòu)圖,。ＴＬＲ４－ＭＤ－２受體是另一種誘發(fā)敗血癥的蛋白質(zhì)。
李知昊說：“了解ＴＬＲ１和ＴＬＲ２基因的形成以及人體的反應(yīng)可以加快目前尋找治療方法的速度,。”全球科學(xué)家一直將ＴＬＲ４和ＴＬＲ２細(xì)胞視為找到敗血癥治療方法的關(guān)鍵,。
李知昊說，ＴＬＲ４細(xì)胞對(duì)感染人體的革蘭氏陰性菌有反應(yīng),，不過ＴＬＲ２則引發(fā)人體對(duì)革蘭氏陽性菌形成自然免疫,。他說，和發(fā)現(xiàn)ＴＬＲ４－ＭＤ－２的過程一樣,，科學(xué)家們使用了“混合ＬＲＲ技術(shù)”,，即用某些蛋白質(zhì)得到ＴＬＲ１和ＴＬＲ２的基因圖。人們期待這一最新發(fā)現(xiàn)可以加快開發(fā)新一代療效更好的敗血癥藥物,。
敗血癥俗稱血中毒,，死亡率在２０％到４０％之間。當(dāng)人體自然免疫系統(tǒng)對(duì)細(xì)菌和病毒感染“反應(yīng)過度”時(shí),，就會(huì)導(dǎo)致敗血癥,。這種反應(yīng)會(huì)誘發(fā)致命性肺衰竭、心衰,、肝衰竭,、腎衰竭以及敗血癥休克。（新華網(wǎng)）
原始出處:
Cell, Vol 130, 1071-1082, 21 September 2007
Article
Crystal Structure of the TLR1-TLR2 Heterodimer Induced by Binding of a Tri-Acylated Lipopeptide
Mi Sun Jin,1 Sung Eun Kim,1,4 Jin Young Heo,1,4 Mi Eun Lee,1 Ho Min Kim,1 Sang-Gi Paik,3 Hayyoung Lee,3 and Jie-Oh Lee1,2,
1 Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejon, Korea 305-701
2 Institute for Bio-Century, Korea Advanced Institute of Science and Technology, Daejon, Korea 305-701
3 Department of Biology, School of Bioscience & Biotechnology, Chungnam National University, Daejon, Korea 305-764
Corresponding author
Jie-Oh Lee
[email protected]
TLR2 in association with TLR1 or TLR6 plays an important role in the innate immune response by recognizing microbial lipoproteins and lipopeptides. Here we present the crystal structures of the human TLR1-TLR2-lipopeptide complex and of the mouse TLR2-lipopeptide complex. Binding of the tri-acylated lipopeptide, Pam3CSK4, induced the formation of an “m” shaped heterodimer of the TLR1 and TLR2 ectodomains whereas binding of the di-acylated lipopeptide, Pam2CSK4, did not. The three lipid chains of Pam3CSK4 mediate the heterodimerization of the receptor; the two ester-bound lipid chains are inserted into a pocket in TLR2, while the amide-bound lipid chain is inserted into a hydrophobic channel in TLR1. An extensive hydrogen-bonding network, as well as hydrophobic interactions, between TLR1 and TLR2 further stabilize the heterodimer. We propose that formation of the TLR1-TLR2 heterodimer brings the intracellular TIR domains close to each other to promote dimerization and initiate signaling.
