Negative stain transmission electron microscopy (TEM) and 2D class averaging analysis of the DVD-Ig^TM molecule alone (upper left) and bound to inner (lower left) and outer antigen (lower right).  In the background is an unprocessed micrograph showing particles that contributed to the class averages. The central figure is a model of the full-length DVD-Ig^TM with IL-18 bound which was constructed using the X-ray structure of the Fab fragment bound to inner antigen. Binding inner antigen (IL-18) causes the outer domain to fold out of plane resulting in a morphological change. Both methods support the extraordinary domain flexibility of the molecule. Image graciously provided by Ivan Correia.