Full-Atom Model of the Agonist LPS-Bound Toll-like Receptor 4 Dimer in a Membrane Environment.

ABSTRACT: The Toll-like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD-2) innate immunity system is a membrane receptor of paramount importance as therapeutic target. Its assembly, upon binding of Gram-negative bacteria lipopolysaccharide (LPS), and also dependent on the membrane composition, finally triggers the immune response cascade. We have combined ab-initio calculations, molecular docking, all-atom molecular dynamics simulations, and thermodynamics calculations to provide the most realistic and complete 3D models of the active full TLR4 complex embedded into a realistic membrane to date. Our studies give functional and structural insights into the transmembrane domain behavior in different membrane environments, the ectodomain bouncing movement, and the dimerization patterns of the in

SUBMITTER: Matamoros-Recio A 

PROVIDER: S-EPMC8596573 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature