4X99

Immunoglobulin Fc heterodimers variant

Summary for 4X99

• Entry DOI: 10.2210/pdb4x99/pdb
• Related: 4X98
• Descriptor: Ig gamma-1 chain C region, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: bispecific antibody, immunoglobulin fc heterodimer, ch3 domain interface, asymmetric disulfide bonds, thermal stability, fc engineering, immune system
• Biological source: Homo sapiens (Human); More
• Cellular location: Secreted: P01857 P01857
• Total number of polymer chains: 2
• Total formula weight: 53101.60

Authors

Seok, S.H.,Choi, H.J.,Kim, Y.J.,Seo, M.D.,Kim, Y.S. (deposition date: 2014-12-11, release date: 2015-06-03, Last modification date: 2023-11-08)

Primary citation

Choi, H.J.,Seok, S.H.,Kim, Y.J.,Seo, M.D.,Kim, Y.S.
Crystal structures of immunoglobulin Fc heterodimers reveal the molecular basis for heterodimer formation.
Mol.Immunol., 65:377-383, 2015

PubMed Abstract: 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-RVT(S-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.

PubMed: 25743157
DOI: 10.1016/j.molimm.2015.02.017

Experimental method

X-RAY DIFFRACTION (2.498 Å)