| First Author | Ju MS | Year | 2015 |
| Journal | Mol Immunol | Volume | 67 |
| Issue | 2 Pt B | Pages | 350-6 |
| PubMed ID | 26153451 | Mgi Jnum | J:233052 |
| Mgi Id | MGI:5780650 | Doi | 10.1016/j.molimm.2015.06.020 |
| Citation | Ju MS, et al. (2015) Structural consequences of aglycosylated IgG Fc variants evolved for FcgammaRI binding. Mol Immunol 67(2 Pt B):350-6 |
| abstractText | In contrast to the glycosylated IgG antibodies secreted by human plasma cells, the aglycosylated IgG antibodies produced by bacteria are unable to bind FcgammaRs expressed on the surface of immune effector cells and cannot trigger immune effector functions. To avoid glycan heterogeneity problems, elicit novel effector functions, and produce therapeutic antibodies with effector function using a simple bacterial expression system, FcgammaRI-specific Fc-engineered aglycosylated antibodies, Fc11 (E382V) and Fc (E382V/M428I), containing mutations in the CH3 region, were isolated in a previous study. To elucidate the relationship between FcgammaRI binding affinity and the structural dynamics of the upper CH2 region of Fc induced by the CH3 mutations, the conformational variation of Fc variants was observed by single-molecule Forster resonance energy transfer (FRET) analysis using alternating-laser excitation (ALEX). In sharp contrast to wild-type Fc, which exhibits a highly dynamic upper CH2 region, the mutations in the CH3 region significantly stabilized the upper CH2 region. The results indicate that conformational plasticity, as well as the openness of the upper CH2 region, is critical for FcgammaR binding and therapeutic effector functions of IgG antibodies. |
