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Published on: July 5, 2018
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Computational design of a pH-sensitive IgG binding protein.
Eva-Maria Strauch1, Sarel J Fleishman, David Baker
1Department of Biochemistry and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195.
Summary
Researchers engineered a novel pH-sensitive protein that binds to immunoglobulin G (IgG). This protein offers controlled binding for applications in purification and diagnostics.
Area of Science:
- Protein engineering
- Computational biology
- Biochemistry
Background:
- Protein-protein interactions are crucial for biological functions.
- Tailoring these interactions computationally offers new therapeutic and diagnostic possibilities.
Purpose of the Study:
- To computationally design a novel protein interface that binds to the Fc domain of immunoglobulin G (IgG) in a pH-dependent manner.
- To characterize the binding properties, stability, and expression of the designed protein.
Main Methods:
- De novo protein interface design was employed.
- Next-generation sequencing was used to analyze a library of design variants.
- Biolayer interferometry was utilized to measure binding affinity at different pH levels.
Main Results:
- A pH-dependent Fc domain binding protein was successfully designed.
- The optimized design exhibited high affinity (Kd ~ 4 nM at pH 8.2) and significantly reduced binding at lower pH (pH 5.5).
- The protein demonstrated exceptional stability, heat resistance, and high expression levels in bacteria.
Conclusions:
- The designed protein enables precise, pH-based control over IgG binding.
- This engineered protein has potential applications in IgG affinity purification and diagnostic devices.
