The Fab conformations in the solution structure of human immunoglobulin G4 (IgG4) restrict access to its Fc region: implications for functional activity.

ABSTRACT: Human IgG4 antibody shows therapeutically useful properties compared with the IgG1, IgG2, and IgG3 subclasses. Thus IgG4 does not activate complement and shows conformational variability. These properties are attributable to its hinge region, which is the shortest of the four IgG subclasses. Using high throughput scattering methods, we studied the solution structure of wild-type IgG4(Ser(222)) and a hinge mutant IgG4(Pro(222)) in different buffers and temperatures where the proline substitution suppresses the formation of half-antibody. Analytical ultracentrifugation showed that both IgG4 forms were principally monomeric with sedimentation coefficients s20,w(0) of 6.6-6.8 S. A monomer-dimer equilibrium was observed in heavy water buffer at low temperature. Scattering showed that the x-ray

SUBMITTER: Rayner LE 

PROVIDER: S-EPMC4110284 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature