Diverse GPCRs exhibit conserved water networks for stabilization and activation.

ABSTRACT: G protein-coupled receptors (GPCRs) have evolved to recognize incredibly diverse extracellular ligands while sharing a common architecture and structurally conserved intracellular signaling partners. It remains unclear how binding of diverse ligands brings about GPCR activation, the common structural change that enables intracellular signaling. Here, we identify highly conserved networks of water-mediated interactions that play a central role in activation. Using atomic-level simulations of diverse GPCRs, we show that most of the water molecules in GPCR crystal structures are highly mobile. Several water molecules near the G protein-coupling interface, however, are stable. These water molecules form two kinds of polar networks that are conserved across diverse GPCRs: (i) a network t

SUBMITTER: Venkatakrishnan AJ 

PROVIDER: S-EPMC6386714 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature