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Updated: Jul 1, 2026
08:58
Characterization of Glycoproteins with the Immunoglobulin Fold by X-Ray Crystallography and Biophysical Techniques
Published on: July 5, 2018
Gas-phase unfolding assay rapidly predicts structure-function relationships in engineered antibodies with tuned
Rosendo C Villafuerte-Vega1,2, Michael R Armbruster1, Hayden Fisher3,4
1Department of Chemistry, University of Michigan, Ann Arbor, MI, USA.
Nature Communications
|June 29, 2026
Summary
Human IgG2 monoclonal antibodies are potent agonists because of hinge region disulfide shuffling. A new collision-induced unfolding assay predicts this agonism, guiding biotherapeutic development.
Area of Science:
- Biochemistry
- Protein Engineering
- Immunology
Background:
- Human (h)IgG2 monoclonal antibodies (mAbs) are recognized as potent agonists.
- Their agonistic activity is partly attributed to disulfide shuffling in their hinge regions.
Purpose of the Study:
- To develop a rapid and sensitive assay for predicting mAb agonism.
- To establish a link between gas-phase protein unfolding and in vivo function.
Main Methods:
- Utilized collision-induced unfolding (CIU) assay to analyze hIgG2 variants.
- Correlated gas-phase unfolding patterns with mAb agonistic activity.
Main Results:
- The CIU assay demonstrated a predictive relationship between unfolding and agonism.
- Identified the significance of hinge engineering in modulating mAb structure-function.
Conclusions:
- Collision-induced unfolding is a valuable tool for assessing mAb agonism.
- Hinge engineering is crucial for optimizing mAb-based biotherapeutics.
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