Exploring electrostatic patterns of human, murine, equine and canine TLR4/MD-2 receptors
| Autor: | Christian Alexander, Minerva González-Melchor, Jorge Lozano-Aponte, Thomas Scior, Francisco Noé Mendoza Ambrosio |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy Protein Conformation Immunology Static Electricity Microbiology Phosphates 03 medical and health sciences chemistry.chemical_compound Molecular dynamics Mice Structure-Activity Relationship 0302 clinical medicine Dogs LPS binding Animals Humans Amino Acid Sequence Horses TLR4 Receptor Molecular Biology Electrostatic interaction phosphate Chemistry Innate immune system Cell Biology Original Articles Electrostatics Phosphate Lipids Immunity Innate molecular modelling Molecular Docking Simulation Toll-Like Receptor 4 030104 developmental biology Infectious Diseases MD-2 Docking (molecular) endotoxicity Biophysics structure–activity relationships lipid IVA lcsh:RC581-607 030215 immunology Protein Binding |
| Zdroj: | Innate Immunity, Vol 26 (2020) Innate Immunity |
| ISSN: | 1753-4267 1753-4259 |
| Popis: | Electrostatic interactions between phosphate anions and Toll-like receptor 4 / Myeloid differentiation factor-2 (TLR4/MD-2) protein complexes of human, murine, equine and canine species were computed. Such knowledge can provide mechanistic information about recognising LPS-like ligands, since anionic phosphate groups belong to the structural features of LPS with their diphosphorylated diglucosamine backbone. Sequence composition analyses, electrostatic interaction potentials and docked energies as well as molecular dynamics studies evaluated the phosphate interactions within the triangular LPS binding site (wedge). According to electrostatic analyses, human, horse and dog wedges possess phosphate-binding sites with indistinct positive and negative charge distributions, but the murine wedge shows a unique strong negative net charge at the site where antagonists bind in other species (Pan). Docking of a phosphate mono-anion (probe) confirmed its repulsion at this Pan site, but the Pag site of the murine wedge attracted the probe. It is occupied by phosphate groups of agonists in other species (Pag). Molecular dynamics trajectories show a variable degree of random walk across the wedges, that is, not following electrostatic preferences (neither Pag nor Pan). In summary, two opposing electrostatic patterns exist –murine versus human, equine and canine species – all of which reflect the potential dual activity mode of under-acylated ligands such as lipid IVA. |
| Databáze: | OpenAIRE |
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