Human immunoglobulin D (IgD) occurs most abundantly as a membrane-bound antibody 
on the surface of mature B cells (mIgD). IgD possesses the longest hinge 
sequence of all the human antibody isotypes, with 64 residues connecting the Fab 
and Fc fragments. A novel rapid purification scheme of secreted IgD from the 
serum of an IgD myeloma patient using thiophilic (T-gel) and lectin affinity 
chromatography gave a stable, homogeneous IgD preparation. Synchrotron X-ray 
scattering and analytical ultracentrifugation of IgD identified the solution 
arrangement of its Fab and Fc fragments, and thereby its hinge structure. The 
Guinier X-ray radius of gyration R(G) of 6.9(+/-0.1)nm showed that IgD is more 
extended in solution than the immunoglobulin subclass IgA1 (R(G) of 6.1-6.2nm). 
Its distance distribution function P(r) showed a single peak at 4.7nm and a 
maximum dimension of 23nm. Velocity experiments gave a sedimentation coefficient 
of 6.3S, which is similar to that for IgA1 at 6.2S. The complete IgD structure 
was modelled using molecular dynamics to generate IgD hinge structures, to which 
homology models for the Fab and Fc fragments were connected. Good scattering 
curve fits were obtained with 18 semi-extended best fit IgD models that were 
filtered from 8500 trial models. These best-fit models showed that the IgD hinge 
does not correspond to an extended polypeptide structure. The averaged solution 
structure arrangement of the Fab and Fc fragments in IgD is principally T-shaped 
and flexible, with contribution from Y-shaped and inverted Y-shaped structures. 
Although the linear sequence of the IgD hinge is much longer, comparison with 
previous scattering modelling of IgA1 and IgA2(m)1 suggests that the hinge of 
IgA1 and IgD are more similar than might have been expected, Both possess 
flexible T-shaped solution structures, probably reflecting the presence of 
restraining O-linked sugars.