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Bradyrhizobium lipid A : immunological properties and molecular basis of its binding to the myeloid differentiation protein-2/toll-like receptor 4 complex

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Abstract
Lipopolysaccharides (LPS) are potent activator of the innate immune response through the binding to the myeloid differentiation protein-2 (MD-2)/toll-like receptor 4 (TLR4) receptor complexes. Although a variety of LPSs have been characterized so far, a detailed molecular description of the structure-activity relationship of the lipid A part has yet to be clarified. Photosynthetic Bradyrhizobium strains, symbiont of Aeschynomene legumes, express distinctive LPSs bearing very long-chain fatty acids with a hopanoid moiety covalently linked to the lipid A region. Here, we investigated the immunological properties of LPSs isolated from Bradyrhizobium strains on both murine and human immune systems. We found that they exhibit a weak agonistic activity and, more interestingly, a potent inhibitory effect on MD-2/TLR4 activation exerted by toxic enterobacterial LPSs. By applying computational modeling techniques, we also furnished a plausible explanation for the Bradyrhizobium LPS inhibitory activity at atomic level, revealing that its uncommon lipid A chemical features could impair the proper formation of the receptorial complex, and/or has a destabilizing effect on the pre-assembled complex itself.
Keywords
BIOLOGICAL-ACTIVITIES, AIRWAY INFLAMMATION, PROPOSED STRUCTURE, INTERFERON-BETA, FORCE-FIELD, LIPOPOLYSACCHARIDE, LPS, RECOGNITION, ANTAGONIST, ACTIVATION, lipopolysaccharide, innate immunity, inflammatory cytokines, myeloid, differentiation protein-2/toll-like receptor 4, Bradyrhizobium lipid A, molecular modeling

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Chicago
Lembo-Fazio, Luigi, Jean-Marc Billod, Flaviana Di Lorenzo, Ida Paciello, Mateusz Pallach, Sara Vaz-Francisco, Aurora Holgado Munoz, et al. 2018. “Bradyrhizobium Lipid A : Immunological Properties and Molecular Basis of Its Binding to the Myeloid Differentiation Protein-2/toll-like Receptor 4 Complex.” Frontiers in Immunology 9.
APA
Lembo-Fazio, L., Billod, J.-M., Di Lorenzo, F., Paciello, I., Pallach, M., Vaz-Francisco, S., Holgado Munoz, A., et al. (2018). Bradyrhizobium lipid A : immunological properties and molecular basis of its binding to the myeloid differentiation protein-2/toll-like receptor 4 complex. FRONTIERS IN IMMUNOLOGY, 9.
Vancouver
1.
Lembo-Fazio L, Billod J-M, Di Lorenzo F, Paciello I, Pallach M, Vaz-Francisco S, et al. Bradyrhizobium lipid A : immunological properties and molecular basis of its binding to the myeloid differentiation protein-2/toll-like receptor 4 complex. FRONTIERS IN IMMUNOLOGY. 2018;9.
MLA
Lembo-Fazio, Luigi et al. “Bradyrhizobium Lipid A : Immunological Properties and Molecular Basis of Its Binding to the Myeloid Differentiation Protein-2/toll-like Receptor 4 Complex.” FRONTIERS IN IMMUNOLOGY 9 (2018): n. pag. Print.
@article{8582316,
  abstract     = {Lipopolysaccharides (LPS) are potent activator of the innate immune response through the binding to the myeloid differentiation protein-2 (MD-2)/toll-like receptor 4 (TLR4) receptor complexes. Although a variety of LPSs have been characterized so far, a detailed molecular description of the structure-activity relationship of the lipid A part has yet to be clarified. Photosynthetic Bradyrhizobium strains, symbiont of Aeschynomene legumes, express distinctive LPSs bearing very long-chain fatty acids with a hopanoid moiety covalently linked to the lipid A region. Here, we investigated the immunological properties of LPSs isolated from Bradyrhizobium strains on both murine and human immune systems. We found that they exhibit a weak agonistic activity and, more interestingly, a potent inhibitory effect on MD-2/TLR4 activation exerted by toxic enterobacterial LPSs. By applying computational modeling techniques, we also furnished a plausible explanation for the Bradyrhizobium LPS inhibitory activity at atomic level, revealing that its uncommon lipid A chemical features could impair the proper formation of the receptorial complex, and/or has a destabilizing effect on the pre-assembled complex itself.},
  articleno    = {1888},
  author       = {Lembo-Fazio, Luigi and Billod, Jean-Marc and Di Lorenzo, Flaviana and Paciello, Ida and Pallach, Mateusz and Vaz-Francisco, Sara and Holgado Munoz, Aurora and Beyaert, Rudi and Fresno, Manuel and Shimoyama, Atsushi and Lanzetta, Rosa and Fukase, Koichi and Gully, Djamel and Giraud, Eric and Martin-Santamaria, Sonsoles and Bernardini, Maria-Lina and Silipo, Alba},
  issn         = {1664-3224},
  journal      = {FRONTIERS IN IMMUNOLOGY},
  keywords     = {BIOLOGICAL-ACTIVITIES,AIRWAY INFLAMMATION,PROPOSED STRUCTURE,INTERFERON-BETA,FORCE-FIELD,LIPOPOLYSACCHARIDE,LPS,RECOGNITION,ANTAGONIST,ACTIVATION,lipopolysaccharide,innate immunity,inflammatory cytokines,myeloid,differentiation protein-2/toll-like receptor 4,Bradyrhizobium lipid A,molecular modeling},
  language     = {eng},
  pages        = {14},
  title        = {Bradyrhizobium lipid A : immunological properties and molecular basis of its binding to the myeloid differentiation protein-2/toll-like receptor 4 complex},
  url          = {http://dx.doi.org/10.3389/fimmu.2018.01888},
  volume       = {9},
  year         = {2018},
}

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