MINITOPICS PROTEINS

Amino Acid Molecular Structures
 Elmhurst College
Immunoglobins Amino Acids  Chemistry Department
Hair - Permanent Wave  Virtual ChemBook





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Immunoglobins

Introduction:

An immunoglobin is a specific protein called an antibody synthesized in response to the presence of a foreign substance (antigen). The antibody has a specific molecular structure capable of recognizing a complementary molecular structure on the antigen which might be some proteins, polysaccharides, and nucleic acids. Small organic foreign molecules do not by themselves elicit antibody formation unless they become bonded to one of the larger biomolecules listed above.

Structure: See graphic on left.

Studies have shown that immunoglobin G (IgG), the most common human immunoglobin, consists of two long "heavy" chains (A and B) and two short "light" chains (C and D). These are in the shape of a Y bonded together with disulfide bonds.

There are several major areas of globular tertiary structure on the chains. The globular structure on the ends of the chains may be variable and accounts for some of the differences in specificity for different antigens. There are also two carbohydrate chains in between the A and B chains.

There are several types of immunoglobins where the composition and structure is slightly different, but still maintains the Y shape. IgG - major serum immunoglobin (antibody).
Ig M - first antibody produced in response to an infection.
IgA - protects body surfaces, mucous membranes, oral cavity.
IgD - thought to regulate antibody synthesis.
IgE - found in larger amounts in people with allergies

Immunoglobin - Chime in new window

 
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Structural Details:

Immunoglobin G (IgG), the most common human immunoglobin, consists of two long "heavy" chains shown as A - cyan and B - magenta in the graphic on the left. There are two disulfide bonds very near the region where the "y" splits. This is also known as the hinge region.

Two short "light" chains shown as C - red and D - green are bonded to the main chains through a single disulfide bond each. There are a a variety of other disulfide bonds in other parts of the molecule as well and observable in the Chime molecule.

In the lower "bulge" region of the main A and B chains, there are two chains of carbohydrates made of glucose and galactose. The carbohydrates are bonded to the protein chain through the amino acid as asparagine. The is through the N of amide side chain to the carbon # 1 in the glucose to make an N-glycosidic bond.

Immunoglobin - Chime in new window


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 Antibody-Antigen Interaction:

The interaction of the antibody with an antigen causes a change in shape of the antibody. The variable regions shown as black or gray in the graphic on the left are the areas of the receptor site for the antigen.

This in turn may cause the exposure of another site which then is responsible for the various reactions elicited by the antibody to destroy the foreign substance. The interaction of antibodies and antigens may produce a network type complex.

Rini, et al.have compared the structures of a Fab fragment of a monoclonal antibody to influenza virus hemagglutinin (HA) in both ligand-bound and unliganded forms.

At the left is displayed the 3-D structure of the V-A and V-C portions of the Fab complexed with the heptapeptide antigen from HA. Examination of the antigen binding pocket reveals that a pronounced conformational change has occurred upon antigen binding. The pocket is deformed by the antigen, closing around it. This is mostly caused by a shift in the orientation of V-A, represented by the gray and red. The red is the orientation of Asp99 and Asn100.

Immunoglobin - Antigen - Chime in new window

Understanding the Immune System - NIH - many pages

Vaccinations:

The understanding of immunochemistry led to the use of vaccinations as protection against various epidemic producing diseases such as small pox, diphtheria, polio, and typhus. A vaccination works by injecting a small amount of weakened disease producing virus into the body which elicits the production of antibodies which eventually destroy the foreign substance. Subsequent invasions of the body by this same virus are met and destroyed by the antibodies formed at the time of vaccination.

Credit: Rini, J.M., Schultze-Gahmen, U., and Wilson, I.A. (1992).
Structural Evidence for Induced Fit as a Mechanism for
Antibody-Antigen Recognition. Science 255: 959-965.