Related Experiment Video
Updated: May 7, 2026

Measuring Nucleotide Binding to Intact, Functional Membrane Proteins in Real Time
Published on: March 11, 2021
GPCR activation: protonation and membrane potential
Xuejun C Zhang1, Kening Sun, Laixing Zhang
1National Laboratory of Macromolecules, National Center for Protein Science-Beijing, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China, zhangc@ibp.ac.cn.
Abstract:
GPCR proteins represent the largest family of signaling membrane proteins in eukaryotic cells. Their importance to basic cell biology, human diseases, and pharmaceutical interventions is well established. Many crystal structures of GPCR proteins have been reported in both active and inactive conformations. These data indicate that agonist binding alone is not sufficient to trigger the conformational change of GPCRs necessary for binding of downstream G-proteins, yet other essential factors remain elusive. Based on analysis of available GPCR crystal structures, we identified a potential conformational switch around the conserved Asp2.50, which consistently shows distinct conformations between inactive and active states. Combining the structural information with the current literature, we propose an energy-coupling mechanism, in which the interaction between a charge change of the GPCR protein and the membrane potential of the living cell plays a key role for GPCR activation.
Related Concept Videos
Activation and Inactivation of G Proteins
IP3/DAG Signaling Pathway
G-Protein Gated Ion Channels
Sensory organs,...
G-protein Coupled Receptors
G-protein Coupled Receptors
GPCRs Regulate Adenylyl Cylase Activity
Two...

