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Updated: Apr 5, 2026
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Author Spotlight: Exploring Cellular Processes by Modeling Ligands in Cryo-EM Maps
Published on: July 19, 2024
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Dynamic monomer-dimer transition in ligand-induced apelin receptor activation
Su-Yu Ji1,2,3,4, Wei-Wei Wang1,2,3,4,5, Yixin Yang1,2,3,4
1Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Nature Communications
|April 3, 2026
Summary
G-protein-coupled receptors (GPCRs) dynamically shift between monomer and dimer forms. This study reveals how ligands and G-proteins control the apelin receptor
Area of Science:
- Biochemistry
- Structural Biology
- Pharmacology
Background:
- G-protein-coupled receptors (GPCRs) are crucial cell signal transducers.
- GPCRs exist as monomers and oligomers, but the mechanism of their interconversion is unclear.
- Understanding GPCR dynamics is vital for deciphering signaling pathways and related diseases.
Purpose of the Study:
- To elucidate the molecular mechanisms governing the monomer-dimer transition in class A GPCRs.
- To provide a dynamic view of the apelin receptor (APLNR) monomer-dimer interconversion.
- To inform rational drug design for selective APLNR signaling modulation.
Main Methods:
- Utilized cryo-electron microscopy (cryo-EM) to determine high-resolution structures.
- Generated and analyzed 12 distinct assemblies of the apelin receptor (APLNR).
- Investigated apo, ligand-bound (small molecule, nanobody), and G-protein-coupled states.
Main Results:
- Different ligands induce varying levels of dimer pre-dissociation in the absence of G-proteins.
- G-protein coupling promotes the transition from dimeric to monomeric APLNR.
- Detailed structural insights into the dynamic regulation of APLNR oligomerization were obtained.
Conclusions:
- Ligand binding and G-protein engagement differentially regulate APLNR oligomeric state.
- GPCR monomer-dimer dynamics are key to intricate signal transduction.
- Findings advance understanding of class A GPCR regulation and drug design for APLNR.
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