Thermal induction of an alternatively folded state in human IgG-Fc.
We report the formation of a non-native, folded state of human IgG4-Fc induced by a high temperature at neutral pH and at a physiological salt concentration. This structure is similar to the molten globule state in that it displays a high degree of secondary structure content and surface-exposed hydrophobic residues. However, it is highly resistant to chemical denaturation. The thermally induced state of human IgG4-Fc is thus associated with typical properties of the so-called alternatively folded state previously described for murine IgG, IgG-Fab, and individual antibody domains (V(L), V(H), C(H)1, and C(H)3) under acidic conditions in the presence of anions. Like some of these molecules, human IgG4-Fc in its alternative fold exists as a mixture of different oligomeric structures, dominated by an equilibrium between monomeric and heptameric species. Heating further induces the formation of fibrous structures in the micrometer range.
Division of Molecular Physics, Department of Physics, Linköping University, SE-581 83 Linköping, Sweden.
Daniel
D
Kanmert
Ann-Christin
AC
Brorsson
Bengt-Harald
BH
Jonsson
Karin
K
Enander
D000906:Antibodies / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry*; D007074:Immunoglobulin G / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D013696:Temperature
D000906:Antibodies; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G