Alternatively Folded State of IgG4: Acid-Induced Compaction is Common between IgG1 and IgG4

Abstract

Immunoglobulin G1 (IgG1) antibodies undergo denaturation in acidic conditions, resulting in an alternatively folded state (AFS). The AFS structure is more compact than the native state. However, the prevalence of AFS in other subclasses remains largely unexplored. This study provides evidence that humanized IgG4 can also adopt AFS structure, as demonstrated through size-exclusion chromatography coupled with small-angle X-ray scattering (SEC-SAXS) analysis. These findings suggest that the anomalous compaction of immunoglobulins G (IgGs) is resilient to variations in sequence and structure among subclasses.