Related Experiment Video
Updated: Mar 17, 2026

Proteomics to Identify Proteins Interacting with P2X2 Ligand-Gated Cation Channels
Published on: May 18, 2009
The Molecular Mechanism of P2Y1 Receptor Activation
Shuguang Yuan1, H C Stephen Chan2, Horst Vogel3
1Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. shuguang.yuan@gmail.com.
Abstract:
Human purinergic G protein-coupled receptor P2Y1 (P2Y1 R) is activated by adenosine 5'-diphosphate (ADP) to induce platelet activation and thereby serves as an important antithrombotic drug target. Crystal structures of P2Y1 R revealed that one ligand (MRS2500) binds to the extracellular vestibule of this GPCR, whereas another (BPTU) occupies the surface between transmembrane (TM) helices TM2 and TM3. We introduced a total of 20 μs all-atom long-timescale molecular dynamic (MD) simulations to inquire why two molecules in completely different locations both serve as antagonists while ADP activates the receptor. Our results indicate that BPTU acts as an antagonist by stabilizing extracellular helix bundles leading to an increase of the lipid order, whereas MRS2500 blocks signaling by occupying the ligand binding site. Both antagonists stabilize an ionic lock within the receptor. However, binding of ADP breaks this ionic lock, forming a continuous water channel that leads to P2Y1 R activation.
More Related Videos
11:47Real-time Live-cell Flow Cytometry to Investigate Calcium Influx, Pore Formation, and Phagocytosis by P2X7 Receptors in Adult Neural Progenitor Cells
Published on: April 3, 2019
08:33Measuring Nucleotide Binding to Intact, Functional Membrane Proteins in Real Time
Published on: March 11, 2021
Related Concept Videos
GPCRs Regulate Adenylyl Cylase Activity
IP3/DAG Signaling Pathway
G-Protein Gated Ion Channels
Sensory...
Amplifying Signals via Second Messengers
Ligand-Gated Ion Channel Receptor: Gating Mechanism
G Protein-coupled Receptors
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...