From agonist to antagonist: Structure and dynamics of innate immune glycoprotein MD-2 upon recognition of variably acylated bacterial endotoxins

Molecular Immunology

Volumn 49, Issue 1-2, 2011, Pages 124-133

  DeMarco, Mari L ^a   Woods, Robert J ^a,b  

^a UNIVERSITY OF GEORGIA   (United States)

^b NATIONAL UNIVERSITY OF IRELAND   (Ireland)

Author keywords

Endotoxin; Lipid A; Lipopolysaccharide; MD 2; Molecular dynamics simulations; TLR4

Indexed keywords

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

ACYLATION; ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; DIMERIZATION; ESCHERICHIA COLI; INNATE IMMUNITY; MOLECULAR DYNAMICS; NEISSERIA MENINGITIDIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN QUATERNARY STRUCTURE; PROTEIN SECONDARY STRUCTURE; PROTEIN TERTIARY STRUCTURE;

ACYLATION; HUMANS; IMMUNITY, INNATE; LIPID A; LYMPHOCYTE ANTIGEN 96; MODELS, MOLECULAR; PROTEIN STRUCTURE, QUATERNARY; PROTEIN STRUCTURE, SECONDARY; PROTEIN STRUCTURE, TERTIARY; TOLL-LIKE RECEPTOR 4;

BACTERIA (MICROORGANISMS); ESCHERICHIA COLI; MAMMALIA; NEGIBACTERIA; NEISSERIA MENINGITIDIS;

EID: 82455198557     PISSN: 01615890     EISSN: 18729142     Source Type: Journal    
DOI: 10.1016/j.molimm.2011.08.003     Document Type: Article

References (52)

1. Akashi S., et al. Lipopolysaccharide interaction with cell surface toll-like receptor 4-MD-2. J. Exp. Med. 2003, 198:1035-1042.
2. Barrett C.P., et al. Dynamite: a simple way to gain insight into protein motions. Acta Crystallogr. D: Biol. Crystallogr. 2004, 60:2280-2287.
3. Bayly C.I., et al. A well-behaved electrostatic potential based method using charge restraints for deriving atomic charges: the RESP model. J. Phys. Chem. 1993, 97:10269-10280.
4. Christ W., et al. E5531, a pure endotoxin antagonist of high potency. Science 1995, 268:80-83.
5. Coats S.R., et al. MD-2 mediates the ability of tetra-acylated and penta-acylated lipopolysaccharides to antagonize Escherichia coli lipopolysaccharide at the TLR4 signaling complex. J. Immunol. 2005, 175:4490-4498.
6. Darden T., et al. Particle mesh Ewald - an Nlog(N) method for Ewald sums in large systems. J. Chem. Phys. 1993, 98:10089-10092.
7. DeMarco M.L., Woods R.J. Atomic-resolution conformational analysis of the GM3 ganglioside in a lipid bilayer and its implications for ganglioside-protein recognition at membrane surfaces. Glycobiology 2009, 19:344-355.
8. Divanovic S., et al. Negative regulation of Toll-like receptor 4 signaling by the Toll-like receptor homolog RP105. Nat. Immunol. 2005, 6:571-578.
9. Ernst R.K., et al. Pseudomonas aeruginosa lipid A diversity and its recognition by Toll-like receptor 4. J. Endotoxin Res. 2003, 9:395-400.
10. Erwin A.L., et al. Enzymatically deacylated Neisseria lipopolysaccharide (LPS) inhibits murine splenocyte mitogenesis induced by LPS. Infect. Immun. 1991, 59:1881-1887.
11. Fransen F., et al. Naturally occurring lipid A mutants in neisseria meningitidis from patients with invasive meningococcal disease are associated with reduced coagulopathy. PLoS Pathog. 2009, 5:e1000396.
12. Frisch M.J., et al. Gaussian 03 2004, Gaussian, Inc., Wallingford, CT.
13. Gioannini T.L., et al. Isolation of an endotoxin-MD-2 complex that produces Toll-like receptor 4-dependent cell activation at picomolar concentrations. Proc. Natl. Acad. Sci. U.S.A. 2004, 101:4186-4191.
14. Gioannini T.L., et al. Monomeric endotoxin: protein complexes are essential for TLR4-dependent cell activation. J. Endotoxin Res. 2005, 11:117-123.
15. Golenbock D.T., et al. Lipid A-like molecules that antagonize the effects of endotoxins on human monocytes. J. Biol. Chem. 1991, 266:19490-19498.
16. Hackett C.J., et al. Monophosphoryl lipid A and synthetic lipid A mimetics as TLR4-based adjuvants and immunomodulators. Vaccine Adjuvants 2006, 235-255. Humana Press. V.S. Georgiev (Ed.).
17. Hadina S., et al. MD-2-dependent pulmonary immune responses to inhaled lipooligosaccharides: effect of acylation state. Am. J. Respir. Cell Mol. Biol. 2008, 38:647-654.
18. Hornak V., et al. Comparison of multiple Amber force fields and development of improved protein backbone parameters. Proteins: Struct. Funct. Bioinf. 2006, 65:712-725.
19. Hubbard S.J., Thornton J.M. 'NACCESS', Computer Program 1993, Department of Biochemistry and Molecular Biology, University College of London.
20. Humphrey W., et al. VMD: visual molecular dynamics. J. Mol. Graph. 1996, 14:33-38.
21. Hyakushima N., et al. Interaction of soluble form of recombinant extracellular TLR4 domain with MD-2 enables lipopolysaccharide binding and attenuates TLR4-mediated signaling. J. Immunol. 2004, 173:6949-6954.
22. Kabsch W., Sander C. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 1983, 22:2577-2637.
23. Kawahara K., et al. Modification of the structure and activity of lipid A in Yersinia pestis lipopolysaccharide by growth temperature. Infect. Immun. 2002, 70:4092-4098.
24. Kawata T., et al. E5531, a synthetic non-toxic lipid A derivative blocks the immunobiological activities of lipopolysaccharide. Br. J. Pharmacol. 1999, 127:853-862.
25. Kim H.M., et al. Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist eritoran. Cell 2007, 130:906-917.
26. Kirschner K.N., et al. GLYCAM06: a generalizable biomolecular force field. Carbohydr. J. Comput. Chem. 2008, 29:622-655.
27. Kobayashi M., et al. Regulatory roles for MD-2 and TLR4 in ligand-induced receptor clustering. J. Immunol. 2006, 176:6211-6218.
28. Mullarkey M., et al. Inhibition of endotoxin response by E5564, a novel Toll-Like receptor 4-directed endotoxin antagonist. J. Pharmacol. Exp. Ther. 2003, 304:1093-1102.
29. Munford R.S., Hall C.L. Detoxification of bacterial lipopolysaccharides (endotoxins) by a human neutrophil enzyme. Science 1986, 234:203-205.
30. Muroi M., Tanamoto K.-i. Structural regions of MD-2 that determine the agonist-antagonist activity of lipid IVa. J. Biol. Chem. 2006, 281:5484-5491.
31. Ohto U., et al. Crystal structures of human MD-2 and its complex with antiendotoxic lipid IVa. Science 2007, 316:1632-1634.
32. Park B.S., et al. The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex. Nature 2009, 458:1191-1195.
33. Pettersen E.F., et al. UCSF chimera - a visualization system for exploratory research and analysis. J. Comput. Chem. 2004, 25:1605-1612.
34. Poltorak A., et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 1998, 282:2085-2088.
35. Raetz C.R.H., et al. Lipid A modification systems in Gram-negative bacteria. Annu. Rev. Biochem. 2007, 76:295-329.
36. Riedo F., et al. Deacylated lipopolysaccharide inhibits plasminogen activator inhibitor-1, prostacyclin, and prostaglandin E2 induction by lipopolysaccharide but not by tumor necrosis factor-alpha. J. Immunol. 1990, 144:3506-3512.
37. Ryckaert J.P., et al. Numerical-integration of Cartesian equations of motion of a system with constraints - molecular-dynamics of N-alkanes. J. Comput. Phys. 1977, 23:327-341.
38. Saitoh S.-i., et al. 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. 2004, 16:961-969.
39. Schletter J., et al. Molecular mechanisms of endotoxin activity. Arch. Microbiol. 1995, 164:383-389.
40. Shimazu R., et al. MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J. Exp. Med. 1999, 189:1777-1782.
41. Spoel D.V.D., et al. GROMACS: fast, flexible, and free. J. Comput. Chem. 2005, 26:1701-1718.
42. Stewart I., et al. Cyanobacterial lipopolysaccharides and human health - a review. Environ. Health 2006, 5:7.
43. Teghanemt A., et al. Novel roles in human MD-2 of phenylalanines 121 and 126 and tyrosine 131 in activation of Toll-like receptor 4 by endotoxin. J. Biol. Chem. 2008, 283:1257-1266.
44. Teghanemt A., et al. Molecular basis of reduced potency of underacylated endotoxins. J. Immunol. 2005, 175:4669-4676.
45. Tessier M.B., et al. Extension of the GLYCAM06 biomolecular force field to lipids, lipid bilayers and glycolipids. Mol. Simul. 2008, 34:349-364.
46. Tidswell M., et al. Phase 2 trial of eritoran tetrasodium (E5564), a Toll-like receptor 4 antagonist, in patients with severe sepsis. Crit. Care Med. 2010, 38:72-83.
47. Walsh C., et al. Elucidation of the MD-2/TLR4 interface required for signaling by lipid IVa. J. Immun. 2008, 181:1245-1254.
48. Wang X., et al. Synthetic and natural TLR4 agonists as safe and effective vaccine adjuvants. Endotoxins: Structure, Function and Recognition 2010, 303-321. Springer, Netherlands. J.R. Harris (Ed.).
49. Wright C.S., et al. Crystal structure analysis of phosphatidylcholine-GM2-activator product complexes: evidence for hydrolase activity. Biochemistry 2005, 44:13510-13521.
50. Zimmer S.M., et al. Human MD-2 discrimination of meningococcal lipid A structures and activation of TLR4. Glycobiology 2007, 17:847-856.
51. Zughaier S., et al. Hexa-acylation and KDO2-glycosylation determine the specific immunostimulatory activity of Neisseria meningitidis lipid A for human monocyte derived dendritic cells. Vaccine 2006, 24:1291.
52. Zughaier S.M., et al. Differential induction of the toll-like receptor 4-MyD88-dependent and -independent signaling pathways by endotoxins. Infect. Immun. 2005, 73:2940-2950.