ABSTRACT
A surprisingly clear picture of the allosteric mechanism connecting G protein-coupled receptor agonists with G protein binding-and back - is revealed by a puzzle of thirty novel 3D structures of the hydroxycarboxylic acid receptor 2 (HCAR2) in complex with eight different orthosteric and a single allosteric agonist. HCAR2 is a sensor of ß-hydroxybutyrate, niacin and certain anti-inflammatory drugs. Surprisingly, agonists with and without on-target side effects bound very similarly and in a completely occluded orthosteric binding site. Thus, despite the many structures we are still left with a pertinent need to understand the molecular dynamics of this and similar systems.
Subject(s)
GTP-Binding Proteins , Protein Binding , Receptors, G-Protein-Coupled , Humans , Ligands , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/chemistry , Receptors, G-Protein-Coupled/agonists , GTP-Binding Proteins/metabolism , Binding Sites , Niacin/metabolism , Niacin/chemistry , Allosteric Regulation , 3-Hydroxybutyric Acid/chemistry , 3-Hydroxybutyric Acid/metabolism , Molecular Dynamics SimulationABSTRACT
Natural transformation is the acquisition of new genetic material via the uptake of exogenous DNA by competent bacteria. Acinetobacter baylyi is model for natural transformation. Here we focus on the natural transformation of A. baylyi ATCC 33305 grown in complex media and seek environmental conditions that appreciably affect transformation efficiency. We find that the transformation efficiency for A. baylyi is a resilient characteristic that remains high under most conditions tested. We do find several distinct conditions that alter natural transformation efficiency including addition of succinate, Fe2+ (ferrous) iron chelation, and substitution of sodium ions with potassium ones. These distinct conditions could be useful to fine tune transformation efficiency for researchers using A. baylyi as a model organism to study natural transformation.