From Construct Design to Structural Insights: A Platform Approach for Challenging GPCR Targets

G protein-coupled receptors (GPCRs) remain among the most important therapeutic target classes, yet their inherent instability, conformational flexibility, and membrane dependence continue to present significant challenges for biochemical and structural characterization. Successful GPCR drug discovery therefore relies on integrated approaches that enable the generation of high-quality receptor samples suitable for a diverse range of downstream applications.

In 2025, we enabled over 20 membrane protein targets and delivered more than 200 cryo-EM-ready samples.

Our approach effectively addresses long-standing technical barriers, paving the way for accelerated structural biology workflows.

In our poster here we describe:

• Our production strategy for GPCRs
  • Application driven workflow
  • Optimization strategy
• How we use FSEC for membrane protein construct screening
• Our tools to increase the stability of a GPCR through engineering
• Techniques we use for the biophysical characterization of membrane proteins

As a proof of principle we describe a cryo-EM case study with serotonin binding and antibody epitope mapping of the 5-HT_2AR.