Gene-to-Structure Workflow for CRBN-DDB1

November 10, 2025

9

min read

Structural insight is essential to the rational design of PROTACs and other targeted protein degraders. Yet obtaining a stable, structure-grade CRBN-DDB1 complex can be a critical challenge—especially when commercially available material is designed for biochemical assays rather than high-resolution structural analysis.

Preparing CRBN-DDB1 for Cryo-EM

This white paper follows an optimized gene-to-structure workflow for co-expression, purification, analytical characterization, and cryo-EM analysis of CRBN-DDB1. It shows how negative-stain TEM, vitrification screening, support-film selection, and data-collection strategy were used to evaluate complex stability and address issues that emerged at the air-water interface.

What You’ll Learn in the White Paper

  • How CRBN and DDB1 expression and purification conditions were optimized
  • Why a complex that appears stable in solution may behave differently after vitrification
  • How grid support, preferred orientation, and conformational flexibility shaped the cryo-EM strategy
  • How unliganded and iberdomide-bound samples informed workflow readiness

Download the white paper to review the complete CRBN-DDB1 workflow and the practical lessons for structure-enabled protein degrader research.

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