Crystal structures of the human IgD Fab reveal insights into CH1 domain diversity

Antibodies of the IgD isotype remain the least well characterized of the mammalian immunoglobulin isotypes. Here we report three-dimensional structures for the Fab region of IgD, based on four different crystal structures, at resolutions of 1.45-2.75 & ANGS;. These IgD Fab crystals provide the first high-resolution views of the unique C81 domain. Structural comparisons identify regions of conformational diversity within the C81 domain, as well as among the homologous domains of C & alpha;1, C & gamma;1 and C & mu;1. The IgD Fab structure also possesses a unique confor-mation of the upper hinge region, which may contribute to the overall disposition of the very long linker sequence between the Fab and Fc regions found in human IgD. Structural similarities observed between IgD and IgG, and differences with IgA and IgM, are consistent with predicted evolutionary relationships for the mammalian antibody isotypes.

Automated summary

This study reveals the three-dimensional structures of the Fab region of IgD, providing insights into the least well characterized mammalian immunoglobulin isotype. It identifies conformational diversity within the C81 domain and structural similarities between IgD and IgG, as well as differences with IgA and IgM, supporting predicted evolutionary relationships among mammalian antibody isotypes. The unique conformation of the upper hinge region in IgD Fab may contribute to the overall disposition of the long linker sequence between the Fab and Fc regions found in human IgD.