Intracellular Transfer of Na⁺ in an Active-State G-Protein-Coupled Receptor.

ABSTRACT: Playing a central role in cell signaling, G-protein-coupled receptors (GPCRs) are the largest superfamily of membrane proteins and form the majority of drug targets in humans. How extracellular agonist binding triggers the activation of GPCRs and associated intracellular effector proteins remains, however, poorly understood. Structural studies have revealed that inactive class A GPCRs harbor a conserved binding site for Na⁺ ions in the center of their transmembrane domain, accessible from the extracellular space. Here, we show that the opening of a conserved hydrated channel in the activated state receptors allows the Na⁺ ion to egress from its binding site into the cytosol. Coupled with protonation changes, this ion movement occurs without significant energy barriers

SUBMITTER: Vickery ON 

PROVIDER: S-EPMC5805466 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature