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.
Bradyrhizobium lipid A: Immunological properties and molecular basis of its binding to the myeloid differentiation protein-2/Toll-like receptor 4 complex / Lembo-Fazio, Luigi; Billod, Jean-Marc; Lorenzo, Flaviana Di; Paciello, Ida; Pallach, Mateusz; Vaz-Francisco, Sara; Holgado, Aurora; Beyaert, Rudi; Fresno, Manuel; Shimoyama, Atsushi; Lanzetta, Rosa; Fukase, Koichi; Gully, Djamel; Giraud, Eric; Martín-Santamaría, Sonsoles; Bernardini, Maria-Lina; Silipo, Alba. - In: FRONTIERS IN IMMUNOLOGY. - ISSN 1664-3224. - ELETTRONICO. - 9:AUG(2018), pp. 1-14. [10.3389/fimmu.2018.01888]
Bradyrhizobium lipid A: Immunological properties and molecular basis of its binding to the myeloid differentiation protein-2/Toll-like receptor 4 complex
Lembo-Fazio, LuigiPrimo
Investigation
;Paciello, IdaInvestigation
;Bernardini, Maria-Lina;
2018
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.File | Dimensione | Formato | |
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