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Identification of interaction sites for dimerization and adapter recruitment in Toll/interleukin-1 receptor (TIR) domain of Toll-like receptor 4

Celia Bovijn (UGent) , Peter Ulrichts (UGent) , Anne-Sophie De Smet (UGent) , Dominiek Catteeuw (UGent) , Rudi Beyaert (UGent) , Jan Tavernier (UGent) and Frank Peelman (UGent)
(2012) JOURNAL OF BIOLOGICAL CHEMISTRY. 287(6). p.4088-4098
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Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
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Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
Abstract
Toll-like receptor signaling requires interactions of the Toll/IL-1 receptor (TIR) domains of the receptor and adapter proteins. Using the mammalian protein-protein interaction trap strategy, homology modeling, and site-directed mutagenesis, we identify the interaction surfaces in the TLR4 TIR domain for the TLR4-TLR4, TLR4-MyD88 adapter-like (MAL), and TLR4-TRIF-related adapter molecule (TRAM) interaction. Two binding sites are equally important for TLR4 dimerization and adapter recruitment. In a model based on the crystal structure of the dimeric TLR10 TIR domain, the first binding site mediates TLR4-TLR4 TIR-TIR interaction. Upon dimerization, two identical second binding sites of the TLR4 TIR domain are juxtaposed and form an extended binding platform for both MAL and TRAM. In our mammalian protein-protein interaction trap assay, MAL and TRAM compete for binding to this platform. Our data suggest that adapter binding can stabilize the TLR4 TIR dimerization.
Keywords
TLR4, DIMER, ACTIVATION, PROTEINS, STRUCTURAL BASIS, INTERACTION TRAP, CRYSTAL-STRUCTURE, SIGNAL-TRANSDUCTION, MULTIPLE SEQUENCE ALIGNMENT, NF-KAPPA-B

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Citation

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MLA
Bovijn, Celia, Peter Ulrichts, Anne-Sophie De Smet, et al. “Identification of Interaction Sites for Dimerization and Adapter Recruitment in Toll/interleukin-1 Receptor (TIR) Domain of Toll-like Receptor 4.” JOURNAL OF BIOLOGICAL CHEMISTRY 287.6 (2012): 4088–4098. Print.
APA
Bovijn, C., Ulrichts, P., De Smet, A.-S., Catteeuw, D., Beyaert, R., Tavernier, J., & Peelman, F. (2012). Identification of interaction sites for dimerization and adapter recruitment in Toll/interleukin-1 receptor (TIR) domain of Toll-like receptor 4. JOURNAL OF BIOLOGICAL CHEMISTRY, 287(6), 4088–4098.
Chicago author-date
Bovijn, Celia, Peter Ulrichts, Anne-Sophie De Smet, Dominiek Catteeuw, Rudi Beyaert, Jan Tavernier, and Frank Peelman. 2012. “Identification of Interaction Sites for Dimerization and Adapter Recruitment in Toll/interleukin-1 Receptor (TIR) Domain of Toll-like Receptor 4.” Journal of Biological Chemistry 287 (6): 4088–4098.
Chicago author-date (all authors)
Bovijn, Celia, Peter Ulrichts, Anne-Sophie De Smet, Dominiek Catteeuw, Rudi Beyaert, Jan Tavernier, and Frank Peelman. 2012. “Identification of Interaction Sites for Dimerization and Adapter Recruitment in Toll/interleukin-1 Receptor (TIR) Domain of Toll-like Receptor 4.” Journal of Biological Chemistry 287 (6): 4088–4098.
Vancouver
1.
Bovijn C, Ulrichts P, De Smet A-S, Catteeuw D, Beyaert R, Tavernier J, et al. Identification of interaction sites for dimerization and adapter recruitment in Toll/interleukin-1 receptor (TIR) domain of Toll-like receptor 4. JOURNAL OF BIOLOGICAL CHEMISTRY. 2012;287(6):4088–98.
IEEE
[1]
C. Bovijn et al., “Identification of interaction sites for dimerization and adapter recruitment in Toll/interleukin-1 receptor (TIR) domain of Toll-like receptor 4,” JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 287, no. 6, pp. 4088–4098, 2012.
@article{2083527,
  abstract     = {Toll-like receptor signaling requires interactions of the Toll/IL-1 receptor (TIR) domains of the receptor and adapter proteins. Using the mammalian protein-protein interaction trap strategy, homology modeling, and site-directed mutagenesis, we identify the interaction surfaces in the TLR4 TIR domain for the TLR4-TLR4, TLR4-MyD88 adapter-like (MAL), and TLR4-TRIF-related adapter molecule (TRAM) interaction. Two binding sites are equally important for TLR4 dimerization and adapter recruitment. In a model based on the crystal structure of the dimeric TLR10 TIR domain, the first binding site mediates TLR4-TLR4 TIR-TIR interaction. Upon dimerization, two identical second binding sites of the TLR4 TIR domain are juxtaposed and form an extended binding platform for both MAL and TRAM. In our mammalian protein-protein interaction trap assay, MAL and TRAM compete for binding to this platform. Our data suggest that adapter binding can stabilize the TLR4 TIR dimerization.},
  author       = {Bovijn, Celia and Ulrichts, Peter and De Smet, Anne-Sophie and Catteeuw, Dominiek and Beyaert, Rudi and Tavernier, Jan and Peelman, Frank},
  issn         = {0021-9258},
  journal      = {JOURNAL OF BIOLOGICAL CHEMISTRY},
  keywords     = {TLR4,DIMER,ACTIVATION,PROTEINS,STRUCTURAL BASIS,INTERACTION TRAP,CRYSTAL-STRUCTURE,SIGNAL-TRANSDUCTION,MULTIPLE SEQUENCE ALIGNMENT,NF-KAPPA-B},
  language     = {eng},
  number       = {6},
  pages        = {4088--4098},
  title        = {Identification of interaction sites for dimerization and adapter recruitment in Toll/interleukin-1 receptor (TIR) domain of Toll-like receptor 4},
  url          = {http://dx.doi.org/10.1074/jbc.M111.282350},
  volume       = {287},
  year         = {2012},
}

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