A collection of images of Ig structures

Basic IgG structure

Schematic image of an IgG

This is a schematic cartoon of an IgG molecule showing some of the features of the molecule including the flexibility of the Fab and Fc regions. This schematic can be compared with the other images shown here which have been rendered from crystal structures of the fragments of Ig molecules.

Immunoglobulin Structures

A complete resolved structure for a human immunoglobulin molecule has only recently been determined. A structure for a whole mouse IgG2a molecule was the first complete immunoglobulin molecule to have been solved. It is surprising to some just how few solved immunoglobulin structures for different species and isotypes of immunoglobulins there are in the database. For practical as well as academic and also commercial reasons many researchers have concentrated their studies on determining the structures of immunoglobulin Fabs and perhaps not surprisingly on their interactions with antigen. Additionaly the interaction of immunoglobulin Fc and Fab regions with bacterial ligands such as Protein A and Protein G have been studied. The models of human IgG1 shown here have in fact been generated by combining several structures in one model and it should be noted and can be seen in the models that the hinge region joining the heavy chain CH1 and CH2 domains is missing. The structures shown here are of a simulated whole IgG1 , the Fc region and the Fab region. Details of how the model was generated are also given.

A Model of human IgG1

  This is a raytraced image of the model of human IgG1 showing the two heavy chains in red, the two light chains in yellow and the carbohydrate attached to the heavy chains in purple. The rotational symmetry about a vertical axis can be clearly seen in this picture.

  This is a cartoon representation of the same model in which the secondary structure of the alpha-carbon backbone trace is shown. The beta strands are indicated as ribbons and can be clearly seen. Note how most of the domains within the structure have one face in intimate contact with a second domain. Thus the heavy and light chain V-region domains are in contact, as are the light chain C region domain and heavy chain CH1 domain, and the two heavy chain CH3 domains. However note the separation of the two heavy chain CH2 domains in the middle of the structure. Evidence suggest that it is the CH2 domains that are of primary importance in determining Fc effector functions such as complement activation (C1q binding) and Fc Receptor (Fc gamma R) binding. However other parts of the molecule may also be critical, in particular the hinge region and hinge link or lower hinge region (where the genetic hinge joins on to a part of the hinge encoded genetically as the N-terminal end of the CH2 domain).

  This is a cartoon of the same model of human IgG1 in which the secondary structure within the model is indicated by both shape and colour. The conserved beta barrel structures making up each immunoglobulin domain along with the beta turns and helical turns at the ends of the beta strands can clearly be identified. If you look carefully you will see that the domain structures for the heavy and light chain V-regions is different from the constant region domains.

The human IgG1 Fc fragment

  This shows a larger view of the secondary structure cartoon of the Fc region from the model. This is based on the alpha carbon trace of the heavy chain and so the carbohydrate which lies between the two CH2 domains cannot be seen. Note the close association of the two CH3 domains.

  In this cartoon the two heavy chains have been coloured in red and blue which makes it much easier to see the contact between the two CH3 domains and if you take a look at the structure below which is rotated you will get an even better idea of the contact.

  Is the same cartoon structure as above but rotated through 90 degrees about a vertical axis showing from a different viewpoint the contact between CH3 domains. Compare the two views and also take a look at the heavy light chain interactions in the Fab structure.

The human IgG1 Fab fragment

  This shows a larger view of a secondary structure cartoon of a single Fab arm from the model which has been coloured according to secondary structure. The contact between V regions and C regions can be clearly seen. The "elbow" bend in the molecule can be made out from the apparent gap in the structure leading from the V-region domains to the C-region domains, joined by a single amino acid strand for each chain. At the bottom left of the structure you can see where the heavy chain would join on to the hinge region.

  Is a cartoon of the other Fab (ie rotated through 180 degrees from the structure above) in which the heavy chain is shown in red and the light chain is a paler colour.

About the model of human IgG1

For the models of human IgG1 shown here I took the coordinates for a crystal structure of a Fab fragment of human IgG1 and a second structure of human IgG1 Fc fragment. The images of a whole antibody are in fact attempts to reconstruct a complete structure from the individual fragments. Firstly I took a structure for a human Fab fragment and cloned it to give two identical copies. One of these copies was then rotated through 180 degrees to simulate a second Fab arm. Then these two Fabs were combined together along with a structure of a human IgG1 Fc fragment to give the appearance of a whole IgG. However the structure of the hinge region has not been determined, presumably because of it's flexible nature, and so this is not shown in the models! The following image shows more clearly the component segments which make up the whole model. The two chains of the Fc, and the four chains making up the two Fab arms, as well as the two chains of carbohydrate, each attached to one of the heavy chains in the Fc fragment, are all coloured separately.

  This shows a representation of the model of Human IgG1 showing the different segments which go to make up the model in different colours.

  Here is raytraced image of the same model of Human IgG1 which gives a better 3D representation to the viewer of a static image. Note the two chains of carbohydrate attached to a conserved site in the CH2. These carbohydrate chains are found within the gap between the two CH2 domains in the structure.

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This page is from signature picture Mike Clark
"An antibody engineer who also enjoys the mountains."
mrc7@cam.ac.uk
Mike's home-page"
10th October 2003