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
Luigi Lembo-FazioAlba Silipo

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.

References

Apr 7, 1995·Science·W J ChristM A Mullarkey
Feb 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·A PoltorakB Beutler
Mar 23, 2000·European Journal of Biochemistry·A B SchrommU Seydel
Feb 28, 2002·Trends in Immunology·Mihai G NeteaJos W M Van der Meer
Apr 24, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Veit HornungGunther Hartmann
Jun 5, 2002·Annual Review of Biochemistry·Christian R H Raetz, Chris Whitfield
Aug 24, 2002·The Journal of Biological Chemistry·Michel L VandenplasJames N Moore
Mar 27, 2004·Proceedings of the National Academy of Sciences of the United States of America·Gail P FergusonGraham C Walker
Apr 30, 2004·Journal of Computational Chemistry·Junmei WangDavid A Case
Dec 21, 2004·Nature Reviews. Microbiology·Samuel I MillerMartin W Bader
Dec 13, 2005·The Journal of Allergy and Clinical Immunology·Doina M Racila, Joel N Kline
Feb 7, 2006·Journal of Molecular Graphics & Modelling·Junmei WangDavid A Case
May 3, 2006·The American Journal of Pathology·Yong Woo JungDavid D Chaplin
Aug 17, 2006·The Journal of Biological Chemistry·Karen E ThomasStefanie N Vogel
Mar 16, 2007·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·D MurakamiY Yoshikai
Jun 2, 2007·Science·Eric GiraudMichael Sadowsky
Jul 10, 2007·Applied and Environmental Microbiology·Cheryl P Andam, Matthew A Parker
Sep 13, 2007·Journal of Computational Chemistry·Karl N KirschnerRobert J Woods
Feb 26, 2008·Nature Immunology·Jonathan C KaganRuslan Medzhitov
Aug 8, 2009·Critical Care Medicine·Mark TidswellUNKNOWN Eritoran Sepsis Study Group
Sep 22, 2009·Trends in Microbiology·Catherine Masson-BoivinJacques Batut
Dec 1, 2009·Nature Reviews. Microbiology·Clare E BryantNicholas J Gay
Jul 2, 2010·The Journal of Biological Chemistry·Jianmin MengDouglas T Golenbock
Aug 16, 2011·Annual Review of Genetics·Giles E D OldroydJ Allan Downie
Mar 1, 2012·FEMS Microbiology Reviews·Kristine von BargenSuzana P Salcedo
Nov 15, 2012·Methods in Molecular Biology·Christian Lück, Jürgen H Helbig
May 3, 2013·Nature·Kari Ann ShireyStefanie N Vogel
Oct 30, 2013·Proceedings of the National Academy of Sciences of the United States of America·Ida PacielloMaria Lina Bernardini
Nov 7, 2013·Proceedings of the National Academy of Sciences of the United States of America·Wenji PiaoVladimir Y Toshchakov
Oct 30, 2014·Chemistry : a European Journal·Antonio MolinaroSonsoles Martín-Santamaría
Nov 6, 2014·The Journal of Biological Chemistry·Iwona KomanieckaOtto Holst

❮ Previous
Next ❯

Citations

Jan 17, 2019·FEMS Microbiology Reviews·Flaviana Di LorenzoAntonio Molinaro
Oct 2, 2020·ACS Central Science·Flaviana Di LorenzoAntonio Molinaro
Aug 29, 2021·Pharmacology & Therapeutics·Pilar Garcia-VelloAntonio Molinaro

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray
Transfection
Assay
ELISA
PCR
acylation

Software Mentioned

LA
HF
PyMOL
AMBER
AutoDockTools
Maestro package
HOLA
GAFF
General Amber GAFF
GLYCAM

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.