9FMB

Crystal structure of human IgD-Fc

Summary for 9FMB

• Entry DOI: 10.2210/pdb9fmb/pdb
• Descriptor: Isoform 1 of Immunoglobulin heavy constant delta, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• Functional Keywords: antibody, immunoglobulin, igd, fc region, immune system
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 109644.41

Authors

Davies, A.M.,McDonnell, J.M. (deposition date: 2024-06-05, release date: 2024-12-04, Last modification date: 2025-03-12)

Primary citation

Davies, A.M.,Bui, T.T.T.,Pacheco-Gomez, R.,Vester, S.K.,Beavil, A.J.,Gould, H.J.,Sutton, B.J.,McDonnell, J.M.
The Crystal Structure of Human IgD-Fc Reveals Unexpected Differences With Other Antibody Isotypes.
Proteins, 93:786-800, 2025

PubMed Abstract: Of the five human antibody isotypes, the function of IgD is the least well-understood, although various studies point to a role for IgD in mucosal immunity. IgD is also the least well structurally characterized isotype. Until recently, when crystal structures were reported for the IgD Fab, the only structural information available was a model for intact IgD based on solution scattering data. We now report the crystal structure of human IgD-Fc solved at 3.0 Å resolution. Although similar in overall architecture to other human isotypes, IgD-Fc displays markedly different orientations of the Cδ3 domains in the Cδ3 domain dimer and the lowest interface area of all the human isotypes. The nature of the residues that form the dimer interface also differs from those conserved in the other isotypes. By contrast, the interface between the Cδ2 and Cδ3 domains in each chain is the largest among the human isotypes. This interface is characterized by two binding pockets, not seen in other isotypes, and points to a potential role for the Cδ2/Cδ3 interface in stabilizing the IgD-Fc homodimer. We investigated the thermal stability of IgD-Fc, alone and in the context of an intact IgD antibody, and found that IgD-Fc unfolds in a single transition. Human IgD-Fc clearly has unique structural features not seen in the other human isotypes, and comparison with other mammalian IgD sequences suggests that these unique features might be widely conserved.

PubMed: 39582378
DOI: 10.1002/prot.26771

Experimental method

X-RAY DIFFRACTION (3 Å)