Crystal Structure of the TLR4-MD-2 Complex with Bound Endotoxin Antagonist Eritoran

Cell

Volumn 130, Issue 5, 2007, Pages 906-917

  Kim, Ho Min ^a   Park, Beom Seok ^a   Kim, Jung In ^a   Kim, Sung Eun ^a   Lee, Judong ^a   Oh, Se Cheol ^a   Enkhbayar, Purevjav ^b   Matsushima, Norio ^c   Lee, Hayyoung ^d   Yoo, Ook Joon ^a   Lee, Jie Oh ^a  

^a Korea Advanced Institute of Science and Technology (KAIST)   (South Korea)

^b NATIONAL UNIVERSITY OF MONGOLIA   (Mongolia)

^c SAPPORO MEDICAL UNIVERSITY   (Japan)

^d Chungnam National University   (South Korea)

Author keywords

MOLIMMUNO; PROTEINS

Indexed keywords

ENDOTOXIN; ERITORAN; LIPOPOLYSACCHARIDE; PROTEIN MD 2; TOLL LIKE RECEPTOR 4; UNCLASSIFIED DRUG;

ARTICLE; BETA SHEET; CONTROLLED STUDY; CRYSTAL STRUCTURE; DIMERIZATION; HAGFISH; HUMAN; MOUSE; MUTAGENESIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; STRUCTURE ANALYSIS;

HAGFISH; NEGIBACTERIA;

EID: 34548222514     PISSN: 00928674     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cell.2007.08.002     Document Type: Article

References (56)

1. Bell J.K., Botos I., Hall P.R., Askins J., Shiloach J., Segal D.M., and Davies D.R. The molecular structure of the Toll-like receptor 3 ligand-binding domain. Proc. Natl. Acad. Sci. USA 102 (2005) 10976-10980
2. Brandenburg K., Hawkins L., Garidel P., Andra J., Muller M., Heine H., Koch M.H., and Seydel U. Structural polymorphism and endotoxic activity of synthetic phospholipid-like amphiphiles. Biochemistry 43 (2004) 4039-4046
3. Brunger A.T., Adams P.D., Clore G.M., DeLano W.L., Gros P., Grosse-Kunstleve R.W., Jiang J.S., Kuszewski J., Nilges M., Pannu N.S., et al. Crystallography & NMR system: A new software suite for macromolecular structure determination. Acta Crystallogr. D Biol. Crystallogr. 54 (1998) 905-921
4. Choe J., Kelker M.S., and Wilson I.A. Crystal structure of human toll-like receptor 3 (TLR3) ectodomain. Science 309 (2005) 581-585
5. Derewenda U., Li J., Derewenda Z., Dauter Z., Mueller G.A., Rule G.S., and Benjamin D.C. The crystal structure of a major dust mite allergen Der p 2, and its biological implications. J. Mol. Biol. 318 (2002) 189-197
6. Friedland N., Liou H.L., Lobel P., and Stock A.M. Structure of a cholesterol-binding protein deficient in Niemann-Pick type C2 disease. Proc. Natl. Acad. Sci. USA 100 (2003) 2512-2517
7. Gay N.J., and Gangloff M. Structure and function of toll receptors and their ligands. Annu. Rev. Biochem. 76 (2007) 141-165
8. Gioannini T.L., Teghanemt A., Zhang D., Coussens N.P., Dockstader W., Ramaswamy S., and Weiss J.P. Isolation of an endotoxin-MD-2 complex that produces Toll-like receptor 4-dependent cell activation at picomolar concentrations. Proc. Natl. Acad. Sci. USA 101 (2004) 4186-4191
9. Gioannini T.L., Teghanemt A., Zhang D., Levis E.N., and Weiss J.P. Monomeric endotoxin:protein complexes are essential for TLR4-dependent cell activation. J. Endotoxin Res. 11 (2005) 117-123
10. Gruber A., Mancek M., Wagner H., Kirschning C.J., and Jerala R. Structural model of MD-2 and functional role of its basic amino acid clusters involved in cellular lipopolysaccharide recognition. J. Biol. Chem. 279 (2004) 28475-28482
11. Hajjar A.M., Ernst R.K., Tsai J.H., Wilson C.B., and Miller S.I. Human Toll-like receptor 4 recognizes host-specific LPS modifications. Nat. Immunol. 3 (2002) 354-359
12. Haziot A., Ferrero E., Lin X.Y., Stewart C.L., and Goyert S.M. CD14-deficient mice are exquisitely insensitive to the effects of LPS. Prog. Clin. Biol. Res. 392 (1995) 349-351
13. He X.L., Bazan J.F., McDermott G., Park J.B., Wang K., Tessier-Lavigne M., He Z., and Garcia K.C. Structure of the Nogo receptor ectodomain: a recognition module implicated in myelin inhibition. Neuron 38 (2003) 177-185
14. Hoshino K., Takeuchi O., Kawai T., Sanjo H., Ogawa T., Takeda Y., Takeda K., and Akira S. Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J. Immunol. 162 (1999) 3749-3752
15. Hyakushima N., Mitsuzawa H., Nishitani C., Sano H., Kuronuma K., Konishi M., Himi T., Miyake K., and Kuroki Y. Interaction of soluble form of recombinant extracellular TLR4 domain with MD-2 enables lipopolysaccharide binding and attenuates TLR4-mediated signaling. J. Immunol. 173 (2004) 6949-6954
16. Inohara N., and Nunez G. ML-a conserved domain involved in innate immunity and lipid metabolism. Trends Biochem. Sci. 27 (2002) 219-221
17. Jiang Z., Georgel P., Du X., Shamel L., Sovath S., Mudd S., Huber M., Kalis C., Keck S., Galanos C., et al. CD14 is required for MyD88-independent LPS signaling. Nat. Immunol. 6 (2005) 565-570
18. Jones T.A., Zou J.Y., Cowan S.W., and Kjeldgaard. Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr. A 47 (1991) 110-119
19. Kajava A.V. Structural diversity of leucine-rich repeat proteins. J. Mol. Biol. 277 (1998) 519-527
20. Kim H.M., Oh S.C., Lim K.J., Kasamatsu J., Heo J.Y., Park B.S., Lee H., Yoo O.J., Kasahara M., and Lee J.O. Structural diversity of the hagfish variable lymphocyte receptors. J. Biol. Chem. 282 (2007) 6726-6732
21. Kim J.I., Lee C.J., Jin M.S., Lee C.H., Paik S.G., Lee H., and Lee J.O. Crystal structure of CD14 and its implications for lipopolysaccharide signaling. J. Biol. Chem. 280 (2005) 11347-11351
22. Kobayashi M., Saitoh S., Tanimura N., Takahashi K., Kawasaki K., Nishijima M., Fujimoto Y., Fukase K., Akashi-Takamura S., and Miyake K. Regulatory roles for MD-2 and TLR4 in ligand-induced receptor clustering. J. Immunol. 176 (2006) 6211-6218
23. Kobe B., and Kajava A.V. The leucine-rich repeat as a protein recognition motif. Curr. Opin. Struct. Biol. 11 (2001) 725-732
24. Landau M., Mayrose I., Rosenberg Y., Glaser F., Martz E., Pupko T., and Ben-Tal N. ConSurf 2005: the projection of evolutionary conservation scores of residues on protein structures. Nucleic Acids Res. 33 (2005) W299-W302
25. Lien E., Means T.K., Heine H., Yoshimura A., Kusumoto S., Fukase K., Fenton M.J., Oikawa M., Qureshi N., Monks B., et al. Toll-like receptor 4 imparts ligand-specific recognition of bacterial lipopolysaccharide. J. Clin. Invest. 105 (2000) 497-504
26. Matsushima N., Tanaka T., Enkhbaya P., Mikami T., Taga M., Ymada K., and Kuroki Y. Comparative sequence analysis of leucine-rich repeats (LRRs) within vertebrate toll-like receptors. BMC Genomics 8 (2007) 124
27. McCoy A.J., Grosse-Kunstleve R.W., Storoni L.C., and Read R.J. Likelihood-enhanced fast translation functions. Acta Crystallogr. D Biol. Crystallogr. 61 (2005) 458-464
28. Medzhitov R., Preston-Hurlburt P., and Janeway Jr. C.A. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388 (1997) 394-397
29. Miyake K. Roles for accessory molecules in microbial recognition by Toll-like receptors. J. Endotoxin Res. 12 (2006) 195-204
30. Mullarkey M., Rose J.R., Bristol J., Kawata T., Kimura A., Kobayashi S., Przetak M., Chow J., Gusovsky F., Christ W.J., and Rossignol D.P. Inhibition of endotoxin response by e5564, a novel Toll-like receptor 4-directed endotoxin antagonist. J. Pharmacol. Exp. Ther. 304 (2003) 1093-1102
31. Muroi M., and Tanamoto K. Structural regions of MD-2 that determine the agonist-antagonist activity of lipid IVa. J. Biol. Chem. 281 (2006) 5484-5491
32. Murshudov G.N., Vagin A.A., and Dodson E.J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D Biol. Crystallogr. 53 (1997) 240-255
33. Nagai Y., Akashi S., Nagafuku M., Ogata M., Iwakura Y., Akira S., Kitamura T., Kosugi A., Kimoto M., and Miyake K. Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nat. Immunol. 3 (2002) 667-672
34. Nishitani C., Mitsuzawa H., Hyakushima N., Sano H., Matsushima N., and Kuroki Y. The Toll-like receptor 4 region Glu24-Pro34 is critical for interaction with MD-2. Biochem. Biophys. Res. Commun. 328 (2005) 586-590
35. Nishitani C., Mitsuzawa H., Sano H., Shimizu T., Matsushima N., and Kuroki Y. Toll-like receptor 4 region Glu24-Lys47 is a site for MD-2 binding: importance of CYS29 and CYS40. J. Biol. Chem. 281 (2006) 38322-38329
36. Ohto U., Fukase K., Miyake K., and Satow Y. Crystal structures of human MD-2 and its complex with antiendotoxic lipid IVa. Science 316 (2007) 1632-1634
37. Otwinowski Z., and Minor W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276 (1997) 307-326
38. Painter J., and Merritt E.A. Optimal description of a protein structure in terms of multiple groups undergoing TLS motion. Acta Crystallogr. D Biol. Crystallogr. 62 (2006) 439-450
39. Poltorak A., He X., Smirnova I., Liu M.Y., Van Huffel C., Du X., Birdwell D., Alejos E., Silva M., Galanos C., et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282 (1998) 2085-2088
40. Poltorak A., Ricciardi-Castagnoli P., Citterio S., and Beutler B. Physical contact between lipopolysaccharide and toll-like receptor 4 revealed by genetic complementation. Proc. Natl. Acad. Sci. USA 97 (2000) 2163-2167
41. Potterton L., McNicholas S., Krissinel E., Gruber J., Cowtan K., Emsley P., Murshudov G.N., Cohen S., Perrakis A., and Noble M. Developments in the CCP4 molecular-graphics project. Acta Crystallogr. D Biol. Crystallogr. 60 (2004) 2288-2294
42. Prohinar P., Re F., Widstrom R., Zhang D., Teghanemt A., Weiss J.P., and Gioannini T.L. Specific high affinity interactions of monomeric endotoxin.protein complexes with Toll-like receptor 4 ectodomain. J. Biol. Chem. 282 (2007) 1010-1017
43. Qureshi S.T., Lariviere L., Leveque G., Clermont S., Moore K.J., Gros P., and Malo D. Endotoxin-tolerant mice have mutations in Toll-like receptor 4 (Tlr4). J. Exp. Med. 189 (1999) 615-625
44. Raetz C.R., and Whitfield C. Lipopolysaccharide endotoxins. Annu. Rev. Biochem. 71 (2002) 635-700
45. Re F., and Strominger J.L. Monomeric recombinant MD-2 binds toll-like receptor 4 tightly and confers lipopolysaccharide responsiveness. J. Biol. Chem. 277 (2002) 23427-23432
46. Re F., and Strominger J.L. Separate functional domains of human MD-2 mediate Toll-like receptor 4-binding and lipopolysaccharide responsiveness. J. Immunol. 171 (2003) 5272-5276
47. Roach J.C., Glusman G., Rowen L., Kaur A., Purcell M.K., Smith K.D., Hood L.E., and Aderem A. The evolution of vertebrate Toll-like receptors. Proc. Natl. Acad. Sci. USA 102 (2005) 9577-9582
48. Rossignol D.P., and Lynn M. TLR4 antagonists for endotoxemia and beyond. Curr. Opin. Investig. Drugs 6 (2005) 496-502
49. Schromm A.B., Lien E., Henneke P., Chow J.C., Yoshimura A., Heine H., Latz E., Monks B.G., Schwartz D.A., Miyake K., and Golenbock D.T. Molecular genetic analysis of an endotoxin nonresponder mutant cell line: a point mutation in a conserved region of MD-2 abolishes endotoxin-induced signaling. J. Exp. Med. 194 (2001) 79-88
50. Shimazu R., Akashi S., Ogata H., Nagai Y., Fukudome K., Miyake K., and Kimoto M. MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J. Exp. Med. 189 (1999) 1777-1782
51. Teghanemt A., Zhang D., Levis E.N., Weiss J.P., and Gioannini T.L. Molecular basis of reduced potency of underacylated endotoxins. J. Immunol. 175 (2005) 4669-4676
52. Viriyakosol S., Tobias P.S., Kitchens R.L., and Kirkland T.N. MD-2 binds to bacterial lipopolysaccharide. J. Biol. Chem. 276 (2001) 38044-38051
53. Visintin A., Latz E., Monks B.G., Espevik T., and Golenbock D.T. Lysines 128 and 132 enable lipopolysaccharide binding to MD-2, leading to Toll-like receptor-4 aggregation and signal transduction. J. Biol. Chem. 278 (2003) 48313-48320
54. Visintin A., Halmen K.A., Latz E., Monks B.G., and Golenbock D.T. Pharmacological inhibition of endotoxin responses is achieved by targeting the TLR4 coreceptor, MD-2. J. Immunol. 175 (2005) 6465-6472
55. Winn M.D. An overview of the CCP4 project in protein crystallography: an example of a collaborative project. J. Synchrotron Radiat. 10 (2003) 23-25
56. Wright C.S., Zhao Q., and Rastinejad F. Structural analysis of lipid complexes of GM2-activator protein. J. Mol. Biol. 331 (2003) 951-964