Structural basis for the multiple interactions of the MyD88 TIR domain in TLR4 signaling

被引:177
作者
Ohnishi, Hidenori [2 ]
Tochio, Hidehito [1 ]
Kato, Zenichiro [2 ,3 ,4 ]
Orii, Kenji E. [2 ]
Li, Ailian [2 ]
Kimura, Takeshi [2 ]
Hiroaki, Hidekazu [5 ]
Kondo, Naomi [2 ,3 ,4 ]
Shirakawa, Masahiro [1 ,6 ]
机构
[1] Kyoto Univ, Dept Mol Engn, Grad Sch Engn, Kyoto 6158510, Japan
[2] Gifu Univ, Dept Pediat, Grad Sch Med, Gifu 5011194, Japan
[3] Gifu Univ, Ctr Emerging Infect Dis, Gifu 5011194, Japan
[4] Gifu Univ, Ctr Adv Drug Res, Gifu 5011194, Japan
[5] Kobe Univ, Grad Sch Med, Div Struct Biol, Chuo Ku, Kobe, Hyogo 6500017, Japan
[6] Japan Sci & Technol Corp, Core Res Evolut Sci & Technol, Kawaguchi, Saitama 3320012, Japan
关键词
docking simulation; Mal; innate immunity; NMR; protein structure; TOLL-LIKE-RECEPTORS; NF-KAPPA-B; ADAPTER MOLECULE; CRYSTAL-STRUCTURE; TRANSDUCTION; TOLL-LIKE-RECEPTOR-4; SPECIFICITY; PREDICTION; DOCKING; PATHWAY;
D O I
10.1073/pnas.0812956106
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Myeloid differentiating factor 88 (MyD88) and MyD88 adaptor-like (Mal) are adaptor molecules critically involved in the Toll-like receptor (TLR) 4 signaling pathway. While Mal has been proposed to serve as a membrane-sorting adaptor, MyD88 mediates signal transduction from activated TLR4 to downstream components. The Toll/Interleukin-1 receptor (TIR) domain of MyD88 is responsible for sorting and signaling via direct or indirect TIR-TIR interactions between Mal and TLR4. However, the molecular mechanisms involved in multiple interactions of the TIR domain remain unclear. The present study describes the solution structure of the MyD88 TIR domain. Reporter gene assays revealed that 3 discrete surface sites in the TIR domain of MyD88 are important for TLR4 signaling. Two of these sites were shown to mediate direct binding to the TIR domain of Mal. Interestingly, Mal-TIR, but not MyD88-TIR, directly binds to the cytosolic TIR domain of TLR4. These observations suggested that the heteromeric assembly of TIR domains of the receptor and adaptors constitutes the initial step of TLR4 intracellular signal transduction.
引用
收藏
页码:10260 / 10265
页数:6
相关论文
共 43 条
  • [41] PREDICTION OF THE STRUCTURE OF A RECEPTOR PROTEIN COMPLEX USING A BINARY DOCKING METHOD
    STODDARD, BL
    KOSHLAND, DE
    [J]. NATURE, 1992, 358 (6389) : 774 - 776
  • [42] Pyogenic bacterial infections in humans with MyD88 deficiency
    von Bernuth, Horst
    Picard, Capucine
    Jin, Zhongbo
    Pankla, Rungnapa
    Xiao, Hui
    Ku, Cheng-Lung
    Chrabieh, Maya
    Ben Mustapha, Imen
    Ghandil, Pegah
    Camcioglu, Yildiz
    Vasconcelos, Julia
    Sirvent, Nicolas
    Guedes, Margarida
    Vitor, Artur Bonito
    Herrero-Mata, Maria Jose
    Arostegui, Juan Ignacio
    Rodrigo, Carlos
    Alsina, Laia
    Ruiz-Ortiz, Estibaliz
    Juan, Manel
    Fortuny, Claudia
    Yague, Jordi
    Anton, Jordi
    Pascal, Mariona
    Chang, Huey-Hsuan
    Janniere, Lucile
    Rose, Yoann
    Garty, Ben-Zion
    Chapel, Helen
    Issekutz, Andrew
    Marodi, Laszlo
    Rodriguez-Gallego, Carlos
    Banchereau, Jacques
    Abel, Laurent
    Li, Xiaoxia
    Chaussabel, Damien
    Puel, Anne
    Casanova, Jean-Laurent
    [J]. SCIENCE, 2008, 321 (5889) : 691 - 696
  • [43] Structural basis for signal transduction by the Toll/interleukin-1 receptor domains
    Xu, YW
    Tao, X
    Shen, BH
    Horng, T
    Medzhitov, R
    Manley, JL
    Tong, L
    [J]. NATURE, 2000, 408 (6808) : 111 - 115