ArticleInternational journal of molecular sciences2023
Cue to Acid-Induced Long-Range Conformational Changes in an Antibody Preceding Aggregation: The Structural Origins of the Subpeaks in Kratky Plots of Small-Angle X-ray Scattering.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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2 authors at 2 institutions in 1 country.
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Abstract
Antibody aggregation, followed by acid denaturation and neutralization of pH, is one of the reasons why the production of therapeutic monoclonal antibodies (mAbs) is expensive. Determining the structural details of acid-denatured antibodies is important for understanding their aggregation mechanism and for antibody engineering. Recent research has shown that monoclonal antibodies of human/humanized immunoglobulin G1 (IgG1) become smaller globules at pH 2 compared to their native structure at pH 7. This acid-denatured species is unstable at pH 7 and prone to aggregation by neutralization of pH. Small-angle X-ray scattering (SAXS) data have revealed an acid-induced reduction in the subpeaks in Kratky plot, indicating conformational changes that can lead to aggregation. The subpeaks are well resolved at pH > 3 but less pronounced at pH ≤ 2. One of the weakened subpeaks indicates loosely organized inter-region (Fab-Fab and Fab-Fc) correlations due to acid denaturation. However, the structural origin of the other subpeak (called
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