A team from the UK, Denmark, and US explore the potential consequences that genetic variation might have on response to drugs targeting G-protein-coupled receptors (GPCRs). For their pharmacogenomic analysis, the researchers brought together genetic variation or mutation data representing drug-targeted GPCRs in almost 68,500 individuals from the Exome Aggregation Consortium, 1000 Genomes Project, or parent-child trios from other studies. Together with structural and functional clues, the genetic data highlighted examples of population variation within GPCR regions related to drug- or effector-binding sites. From these and other data, the authors argue that "characterizing GPCR variants could increase prescription precision, improving patients' quality of life, and relieve the economic and societal burden due to variable drug responsiveness."
Researchers in Switzerland and the US consider protein-metabolite interactions within a chemical proteomic experimental framework. With a so-called chemoproteomic workflow — using LiP-SMap experiments that bring together limited proteolysis and liquid chromatography-coupled tandem mass spectrometry in the presence or absence of interacting small molecules — the team untangled a network of nearly 1,700 metabolite-protein interactions in Escherichia coli, highlighting more than 7,300 potential binding sites. "Our analysis provides a framework to study the effects of metabolite binding on the structure of proteins and protein complexes," they write, "and to evaluate the effect of metabolite concentration on metabolite-protein interactions in the context of the cellular milieu."
An international team describes ties between the maternal microbiome and sex-specific development of embryonic microglia — central nervous system macrophage cells that start as yolk sac macrophages during embryogenesis. Using a combination of expression profiling, chromatin accessibility assays, and microglia density data, the researchers tracked microglia differentiation in male or female mouse embryos developing in germ-free or antibiotics-treated conditions, along with microglia changes in adult mice treated with antibiotics. Based on results from these and other analyses, the authors suggest that microglia "respond to environmental challenges in a sex- and time-dependent manner from prenatal stages, with major implications for our understanding of microglial contributions to health and disease."