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Crystal structures of immunoglobulin Fc heterodimers reveal the molecular basis for heterodimer formation
- Choi, Hye-Ji, Seok, Seung-Hyeon, Kim, Ye-Jin, Seo, Min-Duk, Kim, Yong-Sung
- Molecular Immunology 2015 v.65 pp. 377-383
- X-ray diffraction, antibodies, crystal structure, immunoglobulin G, thermodynamics
- We determined the X-ray crystal structure of an immunoglobulin fragment crystallizable (Fc) heterodimer, EW-RVT, at a resolution of 2.5Å and found that the designed asymmetric interaction residues located in the heterodimeric CH3 interface favor Fc heterodimer formation. We further generated an inter-CH3 disulfide-bonded heterodimeric Fc variant, EW-RVTS–S, which exhibited improved heterodimer formation and thermodynamic stability compared with the parent EW-RVT variant. The crystal structure of EW-RVTS–S superimposed very closely with the wild-type Fc structure. Our results provide the detailed structure of heterodimeric Fc scaffolds, which will be useful for the generation of immunoglobulin G (IgG)-like bispecific antibodies.