Human IgG-Fc Forms an Alternatively Folded State at Low pH
(English)Manuscript (preprint) (Other academic)
Anion-induced formation of so-called alternatively folded states has previously been described for murine IgG, IgG-Fab and several separate antibody domains, including CH3, at low pH. In this report, we confirm that this property can also be extended to the full Fc fragment of IgG. When incubating human IgG4-Fc at pH 2.0 in the presence of NaCl, the protein adopts a conformation that is characterized by a high degree of secondary structure but less well-defined tertiary structure compared to the native state. In contrast to both a classical molten globule and an acid-induced A state, however, the alternatively folded protein appears very stable toward chemical denaturation and unfolds in cooperative transitions. It further forms oligomeric assemblies that are primarily composed of dimers and dodecamers, and when incubated at physiologic temperatures with agitation, it displays prefibrillar structures that are both thioflavinophilic and congophilic.
IdentifiersURN: urn:nbn:se:liu:diva-65533OAI: oai:DiVA.org:liu-65533DiVA: diva2:396466