A combination of scattering and analytical techniques has provided the first atomic-level structural model for the IgG3 antibody
In humans, Immunoglobulin (IgG) is the most common type of antibody found in blood circulation. IgG molecules are created by plasma B cells, and there are four subclasses. Of the four, IgG3 is the least understood. It has a uniquely long hinge region separating its Fab antigen-binding and Fc receptor-binding regions. The presence of this elongated hinge makes it challenging to perform structural studies, for example, with X-ray crystallography. Due to this lack of structural information, IgG3 is the only subclass not currently exploited for therapeutic uses. In work recently published in the Journal of Biological Chemistry, researchers from University College London and the University of Birmingham have used a combination of imaging and analytical methods to provide the first experimentally determined molecular structural model for a full-length IgG3 antibody. This new information should enable the use of IgG3 to develop new therapies and antibody tests.
Getting a good look at IgG3
A high-resolution structure for part of the IgG3 molecule, the globular IgG3-Fc fragment, is available. And previous studies of the whole molecule using Small Angle X-ray Scattering (SAXS) and analytical ultracentrifugation (AUC) showed that IgG3 is elongated compared to IgG1, IgG2 and IgG4. SAXS also showed that IgG3 has a more extended central hinge than IgG1 and IgG2 that links its three globular regions together.
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Image: The IgG3 structural model is formed from two globular Fab regions, a long hinge in the centre, and one Fc region, as shown from the scattering modelling fits. The structure is reminiscent of a giraffe with an extended and semi-rigid neck.
Credit: Dr Valentina Spiteri, UCL.