Structural basis of species-specific endotoxin sensing by innate immune receptor TLR4/MD-2

Proceedings of the National Academy of Sciences of the United States of America

Volumn 109, Issue 19, 2012, Pages 7421-7426

  Ohto, Umeharu ^a,b   Fukase, Koichi ^c   Miyake, Kensuke ^a   Shimizu, Toshiyuki ^a,b  

^a UNIVERSITY OF TOKYO   (Japan)

^b RIKEN Harima Institute Research   (Japan)

^c OSAKA UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ENDOTOXIN; LIPID A; LIPOPOLYSACCHARIDE; PROTEIN MD 2; TOLL LIKE RECEPTOR 4;

ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DIMERIZATION; INNATE IMMUNITY; LIGAND BINDING; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; SPECIES DIFFERENCE;

ANIMALS; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; GLYCOLIPIDS; HUMANS; HYDROPHOBIC AND HYDROPHILIC INTERACTIONS; LIPID A; LIPOPOLYSACCHARIDES; LYMPHOCYTE ANTIGEN 96; MICE; PROTEIN BINDING; PROTEIN MULTIMERIZATION; PROTEIN STRUCTURE, QUATERNARY; PROTEIN STRUCTURE, TERTIARY; SCATTERING, SMALL ANGLE; SPECIES SPECIFICITY; STATIC ELECTRICITY; TOLL-LIKE RECEPTOR 4; X-RAY DIFFRACTION;

IVA;

EID: 84860832650     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1201193109     Document Type: Article

References (36)

1. Janeway CA, Jr., Medzhitov R (2002) Innate immune recognition. Annu Rev Immunol 20:197-216.
2. Gay NJ, Gangloff M (2007) Structure and function of Toll receptors and their ligands. Annu Rev Biochem 76:141-165.
3. Poltorak A, et al. (1998) Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: Mutations in Tlr4 gene. Science 282:2085-2088. (Pubitemid 29001265)
4. Nagai Y, et al. (2002) Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nat Immunol 3:667-672. (Pubitemid 34752476)
5. Angus DC, et al. (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29:1303-1310. (Pubitemid 32641789)
6. Rangel-Frausto MS (2005) Sepsis: Still going strong. Arch Med Res 36:672-681.
7. Schletter J, Heine H, Ulmer AJ, Rietschel ET (1995) Molecular mechanisms of endotoxin activity. Arch Microbiol 164:383-389. (Pubitemid 26018509)
8. Raetz CR, Whitfield C (2002) Lipopolysaccharide endotoxins. Annu Rev Biochem 71: 635-700. (Pubitemid 34800232)
9. Rietschel ET, et al. (1994) Bacterial endotoxin: Molecular relationships of structure to activity and function. FASEB J 8:217-225.
10. Rietschel ET, et al. (1993) The chemical structure of bacterial endotoxin in relation to bioactivity. Immunobiology 187:169-190. (Pubitemid 23150766)
11. Shimazu R, et al. (1999) MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J Exp Med 189:1777-1782. (Pubitemid 29272694)
12. Inohara N, Nuñez G (2002) ML-a conserved domain involved in innate immunity and lipid metabolism. Trends Biochem Sci 27:219-221. (Pubitemid 34655436)
13. Viriyakosol S, Tobias PS, Kitchens RL, Kirkland TN (2001) MD-2 binds to bacterial lipopolysaccharide. J Biol Chem 276:38044-38051.
14. Park BS, et al. (2009) The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex. Nature 458:1191-1195.
15. Jin MS, Lee JO (2008) Structures of the toll-like receptor family and its ligand complexes. Immunity 29:182-191.
16. Kumar H, Kawai T, Akira S (2009) Toll-like receptors and innate immunity. Biochem Biophys Res Commun 388:621-625.
17. Homma JY, Matsuura M, Kumazawa Y (1990) Structure-activity relationship of chemically synthesized nonreducing parts of lipid A analogs. Adv Exp Med Biol 256: 101-119. (Pubitemid 20244400)
18. Takada H, Kotani S (1989) Structural requirements of lipid A for endotoxicity and other biological activities. Crit Rev Microbiol 16:477-523.
19. Fujimoto Y, et al. (2005) Synthesis of lipid A and its analogues for investigation of the structural basis for their bioactivity. J Endotoxin Res 11:341-347. (Pubitemid 41724230)
20. Raetz CR, Reynolds CM, Trent MS, Bishop RE (2007) Lipid A modification systems in gram-negative bacteria. Annu Rev Biochem 76:295-329.
21. Golenbock DT, Hampton RY, Qureshi N, Takayama K, Raetz CR (1991) Lipid A-like molecules that antagonize the effects of endotoxins on human monocytes. J Biol Chem 266:19490-19498. (Pubitemid 21908258)
22. Muroi M, Tanamoto K (2006) Structural regions of MD-2 that determine the agonistantagonist activity of lipid IVa. J Biol Chem 281:5484-5491. (Pubitemid 43847643)
23. Saitoh S, et al. (2004) Lipid A antagonist, lipid IVa, is distinct from lipid A in interaction with Toll-like receptor 4 (TLR4)-MD-2 and ligand-induced TLR4 oligomerization. Int Immunol 16:961-969. (Pubitemid 38960874)
24. Hajjar AM, Ernst RK, Tsai JH, Wilson CB, Miller SI (2002) Human Toll-like receptor 4 recognizes host-specific LPS modifications. Nat Immunol 3:354-359. (Pubitemid 34308623)
25. Vasl J, Oblak A, Gioannini TL, Weiss JP, Jerala R (2009) Novel roles of lysines 122, 125, and 58 in functional differences between human and murine MD-2. J Immunol 183: 5138-5145.
26. Meng J, Drolet JR, Monks BG, Golenbock DT (2010) MD-2 residues tyrosine 42, arginine 69, aspartic acid 122, and leucine 125 provide species specificity for lipid IVA. J Biol Chem 285:27935-27943.
27. Meng J, Lien E, Golenbock DT (2010) MD-2-mediated ionic interactions between lipid A and TLR4 are essential for receptor activation. J Biol Chem 285:8695-8702.
28. Walsh C, et al. (2008) Elucidation of the MD-2/TLR4 interface required for signaling by lipid IVa. J Immunol 181:1245-1254.
29. Prohinar P, et al. (2007) Specific high affinity interactions of monomeric endotoxin. protein complexes with Toll-like receptor 4 ectodomain. J Biol Chem 282:1010-1017. (Pubitemid 47076551)
30. Kim HM, et al. (2007) Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran. Cell 130:906-917. (Pubitemid 47332573)
31. Xu Y, et al. (2000) Structural basis for signal transduction by the Toll/interleukin-1 receptor domains. Nature 408:111-115.
32. Nyman T, et al. (2008) The crystal structure of the human toll-like receptor 10 cytoplasmic domain reveals a putative signaling dimer. J Biol Chem 283:11861-11865.
33. Yoon SI, et al. (2012) Structural basis of TLR5-flagellin recognition and signaling. Science 335:859-864.
34. Ohto U, Fukase K, Miyake K, Satow Y (2007) Crystal structures of human MD-2 and its complex with antiendotoxic lipid IVa. Science 316:1632-1634. (Pubitemid 46982039)
35. Kobayashi M, et al. (2006) Regulatory roles for MD-2 and TLR4 in ligand-induced receptor clustering. J Immunol 176:6211-6218.
36. Resman N, et al. (2009) Essential roles of hydrophobic residues in both MD-2 and tolllike receptor 4 in activation by endotoxin. J Biol Chem 284:15052-15060.