13.1B: Antibody Structure - Biology

13.1B: Antibody Structure - Biology

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Learning Objectives

  1. Describe an antibody molecule.
  2. Draw the "stick figure" structure of IgG, indicating the Fab portion (variable region) and the Fc portion (constant region).
  3. State the functions of the Fab and the Fc portions of an antibody.
  4. State what is meant by the biological activity of an antibody.
  5. Compare the structure of IgM and secretory IgA with that of IgG.

In this section we will look at the structure of antibodies. There are five classes or isotypes of human antibodies :

  1. immunoglobulin G (IgG),
  2. immunoglobulin M (IgM),
  3. immunoglobulin A (IgA),
  4. immunoglobulin D (IgD), and
  5. immunoglobulin E (IgE).

The simplest antibodies, such as IgG, IgD, and IgE, are "Y"-shaped macromolecules called monomers. A monomer is composed of four glycoprotein chains: two identical heavy chains and two identical light chains. The two heavy chains have a high molecular weight that varies with the class of antibody. The light chains come in two varieties: kappa or lambda and have a lower molecular weight than the heavy chains. The four glycoprotein chains are connected to one another by disulfide (S-S) bonds and non-covalent bonds (Figure (PageIndex{1})).

Additional S-S bonds fold the individual glycoprotein chains into a number of distinct globular domains (Figure (PageIndex{2})). The area where the top of the "Y" joins the bottom is called the hinge. This area is flexible to enable the antibody to bind to pairs of epitopes various distances apart on an antigen.

The two tips of the "Y" monomer are referred to as the antigen-binding fragments or Fab portions of the antibody (Figures 1-3). The first 110 amino acids or first domain of both the heavy and light chain of the Fab region of the antibody provide specificity for binding an epitope on an antigen. The amino acid sequence of this first domain of both the light chain and the heavy chain shows tremendous variation from antibody to antibody and constitutes the variable region (V region). This is because each B-lymphocyte, early in its development, becomes genetically programmed through a series of gene-splicing reactions to produce a Fab with a unique 3-dimensional shape capable of fitting some epitope with a corresponding shape.

Figure (PageIndex{3}): Ribbon Drawing of the Antibody Molecule IgG2a, A ribbon drawing of the first intact antibody molecule ever crystallized (IgG2a). The Fab portion of the antibody has specificity for binding an epitope of an antigen. The Fc portion directs the biological activity of the antibody.

The various genes the cell splices together determine the order of amino acids of the Fab portion of both the light and heavy chain; the amino acid sequence determines the final 3-dimensional shape (Figure (PageIndex{4})). Therefore, different antibody molecules produced by different B-lymphocytes will have different orders of amino acids at the tips of the Fab to give them unique shapes for binding epitope. The antigen-binding site is large enough to hold an epitope of about 5-7 amino acids or 3-4 sugar residues. Epitopes bind to the Fab portion of the antibody by reversible, non-covalent bonds.

The bottom part of the "Y", the C terminal region of each glycoprotein chain, is called the Fc portion. The Fc portion, as well as one domain of both the heavy and light chain of the Fab region has a constant amino acid sequence and is referred to as the constant region (C region) of the antibody and defines the class and subclass of each antibody. The Fc portion is responsible for the biological activity of the antibody (Figures 1-3), however, the Fc portion only becomes biologically active after the Fab component has bound to its corresponding antigen. Depending on the class and subclass of antibody, biological activities of the Fc portion of antibodies include the ability to:

  • Activate the classical complement pathway (IgG & IgM); see Figure (PageIndex{5}).
  • Activate the lectin complement pathway and the alternative complement pathway (IgA)
  • Bind to receptors on phagocytes (IgG); see Figure (PageIndex{6}).
  • Bind to receptors on mast cells, basophils, and eosinophils (IgE); see Fig 7 and Figure (PageIndex{8}).
  • Bind to receptors on NK cells (IgG); see Figure (PageIndex{9}).
  • Determine the tissue distribution of the antibodies, that is, to what tissues types the antibody molecules are able to go.

Individual "Y"-shaped antibody molecules are called monomers and can bind to two identical epitopes. Antibodies of the classes IgG, IgD, and IgE are monomers.

Two classes of antibodies are more complex. IgM (see Figure (PageIndex{10})) is a pentamer, consisting of 5 "Y"-like molecules connected at their Fc portions by a "J" or joining chain. Secretory IgA (see Figure (PageIndex{11})) is a dimer consisting of 2 "Y"-like molecules connected at their Fc portions by a "J" chain and stabilized to resist enzymatic digestion in body secretions by means of a secretory component.


  1. There are 5 classes or isotypes of human antibodies or immunoglobulins: IgG, IgM, IgA, IgD, and IgE.
  2. The simplest antibodies, such as IgG, IgD, and IgE, are "Y"-shaped macromolecules called monomers and are composed of four glycoprotein chains: two identical heavy chains and two identical light chains.
  3. The two tips of the "Y" monomer are referred to as the antigen-binding fragments or Fab portions of the antibody and these portions provide specificity for binding an epitope on an antigen.
  4. Early in its development, each B-lymphocyte becomes genetically programmed through a series of gene-splicing reactions to produce a Fab with a unique 3-dimensional shape capable of fitting some epitope with a corresponding shape.
  5. The Fc portion only becomes biologically active after the Fab component has bound to its corresponding antigen. Biological activities include activating the complement pathways, and binding to receptors on phagocytes and other defense cells to promote adaptive immunity.
  6. IgM is a pentamer, consisting of 5 monomers joined at their Fc portions.
  7. IgA is a dimer, consisting of 2 monomers joined at their Fc portions.


Study the material in this section and then write out the answers to these questions. Do not just click on the answers and write them out. This will not test your understanding of this tutorial.

  1. Describe an antibody molecule. (ans)
  2. Match the following:

    _____ The region of the antibody that provide specificity for binding an epitope on an antigen. (ans)

    _____ The region of the antibody that is responsible for the biological activity of the antibody. (ans)

    _____ Composed of four glycoprotein chains. There are two identical heavy chains having a high molecular weight and two identical light chains. (ans)

    _____ A pentamer, consisting of 5 "Y"-like molecules connected at their Fc portions by a "J" or joining chain. (ans)

    _____ A dimer consisting of 2 "Y"-like molecules connected at their Fc portions by a "J" chain and stabilized to resist enzymatic digestion. (ans)

    1. IgM
    2. secretory IgA
    3. IgG
    4. Fab
    5. Fc
  3. Multiple Choice (ans)


NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Janeway CA Jr, Travers P, Walport M, et al. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science 2001.

  • By agreement with the publisher, this book is accessible by the search feature, but cannot be browsed.

Antibodies: Meaning, Structure and Mechanism

Antibodies, the magic bullets of the immune system, are glycoproteins formed in response to antigenic stimulation and counteract with antigens with great specificity.

The antibodies are found in the serum fraction of the blood and are also known as immunoglobulins (Ig). The chemical composition and structure of antibodies was revealed by G.M. Edelman and R.M. Porter who received in 1972 Nobel Prize in Physiology and Medicine for this contribution.

Structure of Antibodies:

Antibodies (immunoglobulins) have molecular weights ranging from 150,000 to 900,000 daltons. Electron microscopic viewing reveals that the antibody molecules resemble the letter “T” before they combine with antigens (Fig. 41.6A) while they resemble the letter “Y” after antigens combine with them (Fig. 41.6B).

It is considered that the antigen-antibody binding causes a rearrangement in the T-shape structure of the antibody molecule resulting in Y-shape thus providing more exposure to complement binding site of heavy-chain for further reactions.

An immunoglobulin (antibody) molecule is composed of four polypeptide chains (Fig. 41.7). Two of the four chains are identical to each other and are called heavy (H) chains because of greater number of amino acids (approximately 440 amino acids in each chain) and thus high molecular weight (approximately 50,000 daltons).

The remaining two chains, also identical to each other, are termed light (L) chains because of lesser number of amino acids, (approximately 440 amino acids in each chain) and thus low molecular weight (approximately 23,000 daltons). Each antibody molecule consists of a stem-part and two arms.

The stem-part of the antibody molecule is formed by approximately one-half of each heavy-chain, and the two chains are joined together by sulphur to sulphur (disulphide) bonds. Each arm of the antibody molecule consists of approximately one-half of a heavy-chain and one light-chain, again joined by a disulphide bond.

Both, light and heavy-chains also possess intrachain disulphide bonds that create “loops”, each loop called a domain. Each light-chain contains a single variable-domain (VL) and a single constant-domain (CL) whereas each heavy-chain contains a singly variable-domain (VH) and three, sometimes, four constant-domains (CH1, CH2, CH3 and in some cases CH4).

The variable-domains form the variable (V) region while the constant-domains form the constant (C) region of each of the light and heavy-chains. Variable (V) regions of both the chains lie opposite to each other at the top of the two arms of the antibody molecule and represent the site where the antigen-antibody-binding takes place.

Remaining part of each of the chains represents the constant (C) region which varies in different class of antibodies with respect to its amino acid sequence, and thus determines the type of antigen-antibody reaction.

Classes of Antibodies:

All immunoglobulins (antibodies) physicochemical properties vary considerably because of variations in amino acid sequence in their heavy polypeptide chain. Therefore, according to their physicochemical properties, the immunoglobulins are subdivided into five different classes, namely, IgG, IgA, IgM, IgD, and IgE (Table 41.6).

Mechanism of Antibody Formation: Clonal Selection Theory:

These are the B-lymphocytes that produce antibodies in the body. Various theories have been proposed regarding the formation of antibodies, it is the clonal selection theory which has gained wide support. This theory states that there are a variety of B- lymphocytes present in the immune system.

These lymphocytes produce a small number of antibody molecules without any antigenic stimulation, and these antibody molecules integrate into the cytoplasmic membrane of their producer lymphocyte to serve as receptor site for specific antigen. When specific antigens enter the immune system, they interact only with complementary antibody- receptor site of B-lymphocyte.

In this way, such B-lymphocyte is “selected out” or “differentiated” by the union of specific antigen and its complementary antibody. This “selected out” or “differentiated” B-lymphocyte is stimulated to undergo multiplication leading to clones of plasma cells which synthesize and secrete a crop of antibodies complementary’ to the specific antigens that have entered the immune system.

In fact, the “selected out” or “differentiated” B-lymphocytes initiate multiplication forming two different cell populations: the primary B-lymphocytes and the secondary B-lymphocytes.

The primary, in response to antigenic stimulation, divide and transform into plasma cells which enter into the process of antibody formation, but the secondary B- lymphocytes do not. The latter circulate actively from blood to lymph and liver, and constitute memory cells.

These memory cells, however, transform into plasma cells when they are exposed to subsequent antigenic stimulation, perhaps years later, and enter into the process of antibody formation (Fig. 41.8A).

The B-lymphocytes get transformed into antibody-synthesizing mature plasma cells through a prolonged process (Fig. 41.8B). It has been revealed that a transformation period of about five days involving at-least eight successive cell generations is required for the formation of mature plasma cells from the B-lymphocyte cells.

With each cell generation, there is a progressive development of ribosomes and endoplasmic reticulum. By the fifth day, the RNA content of the plasma cell is very much increased and its entire protein synthesizing machinery is so activated that the endoplasmic reticulum cisternae are filled with antibody molecules, and the plasma cells rapidly secrete them.

It is estimated that about 90-95% of the total protein produced in plasma cells gives rise to antibodies, and about 10,000 antibody molecules are secreted per plasma cell per second. However, obviously thousands of plasma cells throughout the circulatory system are in operation for the production of antibodies at any given time.

13.1B: Antibody Structure - Biology

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1. Janeway Jr, C. A., Travers, P., Walport, M., & Shlomchik, M. J. (2001). The structure of a typical antibody molecule. In Immunobiology: The Immune System in Health and Disease. 5th edition. Garland Science.
2. Chen, K., & Cerutti, A. (2011). The function and regulation of immunoglobulin D. Current opinion in immunology, 23(3), 345-352.
3. Solomon, A., & Weiss, D. T. (1995). Structural and functional properties of human lambda-light-chain variable-region subgroups. Clinical and diagnostic laboratory immunology, 2(4), 387.

Classes of immunoglobulins

The five primary classes of immunoglobulins are IgG, IgM, IgA, IgD and IgE. These are distinguished by the type of heavy chain found in the molecule. IgG molecules have heavy chains known as gamma-chains IgMs have mu-chains IgAs have alpha-chains IgEs have epsilon-chains and IgDs have delta-chains.

Differences in heavy chain polypeptides allow these immunoglobulins to function in different types of immune responses and at particular stages of the immune response. The polypeptide protein sequences responsible for these differences are found primarily in the Fc fragment. While there are five different types of heavy chains, there are only two main types of light chains: kappa (κ) and lambda (λ).

Antibody classes differ in valency as a result of different numbers of Y-like units (monomers) that join to form the complete protein. For example, in humans, functioning IgM antibodies have five Y-shaped units (pentamer) containing a total of 10 light chains, 10 heavy chains and 10 antigen-binding.

IgG class

  • Molecular weight: 150,000
  • H-chain type (MW): gamma (53,000)
  • Serum concentration: 10 to 16 mg/mL
  • Percent of total immunoglobulin: 75%
  • Glycosylation (by weight): 3%
  • Distribution: intra- and extravascular
  • Function: secondary response

IgM class

  • Molecular weight: 900,000
  • H-chain type (MW): mu (65,000)
  • Serum concentration: 0.5 to 2 mg/mL
  • Percent of total immunoglobulin: 10%
  • Glycosylation (by weight): 12%
  • Distribution: mostly intravascular
  • Function: primary response

IgA class

  • Molecular weight: 320,000 (secretory)
  • H-chain type (MW): alpha (55,000)
  • Serum concentration: 1 to 4 mg/mL
  • Percent of total immunoglobulin: 15%
  • Glycosylation (by weight): 10%
  • Distribution: intravascular and secretions
  • Function: protect mucus membranes

IgD and IgE class

  • Molecular weight: 180,000
  • H-chain type (MW): delta (70,000)
  • Serum concentration: 0 to 0.4 mg/mL
  • Percent of total immunoglobulin: 0.2%
  • Glycosylation (by weight): 13%
  • Distribution: lymphocyte surface
  • Function: unknown
  • Molecular weight: 200,000
  • H-chain type (MW): epsilon (73,000)
  • Serum concentration: 10 to 400 ng/mL
  • Percent of total immunoglobulin: 0.002%
  • Glycosylation (by weight): 12%
  • Distribution: basophils and mast cells in saliva and nasal secretions
  • Function: protect against parasites

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Structure-based Antibody Reformatting

The antigen binding regions of an antibody (variable heavy and light chain genes) are able to be isolated using phage display. Apart from altering the Fc portion of an antibody, the variable region of an immunoglobulin enables to be reformatted into a number of different fragments, including Fab, F(ab)’2, scFv, VHH, and minibodies. Due to their smaller antibody formats, increased tumour/tissue penetration, as well as relative ease of expression in non-mammalian systems, they play an increasingly important role in drug discovery and clinical research. As an undisputed lead in the antibody engineering area, Creative Biolabs provides a full range of structure-based antibody reformatting services by using in silico technology.

In silico Design for Antibody Reformatting

Generally, in order to obtain an ideal antibody fragment with good stability, high affinity, and preeminent specificity, a serious of reform procedures are required before the antibody production. Therefore, we have developed a full range of in silico techniques for antibody design and reformatting.

  • Homology modeling
  • Molecular dynamics simulation
  • In-house algorithm
  • Antibody molecule model analysis

By using these in silico techniques, we are able to identification the main residues affecting a certain characteristic of the target antibody. After that, appropriate mutations can be made on these residues to alter the antibody properties. In this way, the target antibody molecule can maintain a relatively stable physicochemical property after reformat and keep the original affinity and function. In addition, the external environment of the modified molecular model can be set up, and which can be evaluating by RMSD, RMSF, as well as the potential energy inside the molecule.

Fig 1. Schematic representation of the HuLys11 scFv (pdb 1BVK).

The Variable Region Engineering for Reformatting

We developed several approaches to facilitate the variable region engineering for reformatting antibody, including:

  • Engineering the antigen binding properties in silico
    Generally, computational design is based on two capabilities: accurate energetic evaluation and conformational search. Antigen binding properties design mainly refers to affinity maturation, altering the specificity.
  • Improving the pharmacokinetics: isoelectric point engineering and engineering PH dependency.
  • Improving the Pharmaceutical Properties: thermal stability improvement, solubility improvement, chemical stability improvement, and heterogeneity improvement.
  • Reducing the Immunogenicity
    At present, a variety of in silico tools to predict effector T-cell epitopes have been designed, including iTope/TCED (Antitope Ltd.,), Epibase (AlgoNomics NV), and EpiMatrix (EpiVax Inc.,). Based on these advanced in silico tools, the presence of effector T-cell epitope in each antibody sequence are able to be predicted, making the potential immunogenicity of the antibody therapeutics to be decreased by selecting a sequence with the minimum number of effector T-cell epitopes.

Reformat into scFv and VHH

Currently, the success of antibody therapeutics has led to the rapid development of novel therapeutic antibody forms, such as scFv and VHH. Researchers develop so-called second or third generation antibodies with clinical differentiation by using various engineering and optimization technologies. Antibody variable region is responsible to bind antigen, however, it is also the major source of antibody diversity and its sequence affects a number of properties important for developing antibody therapeutics. Besides, the CDR3 length of camelid antibodies is significantly greater than that of classical antibodies for use as starting points for peptidomimetic and small molecule design, as reagents for cell biology or as potential therapeutic agents. Creative Biolabs provide high quality reformatting into scFv and VHH services with optimal variable region and molecule model.

  • scFv
    Currently, generation of single-chain fragment variable (scFv) has become a common strategy applied to generate a completely functional antigen-binding fragment in bacterial systems. Besides, the scFv antibody fragments can also be used in the construction of immunotoxins, therapeutic gene delivery, as well as anticancer intrabodies for therapeutic purposes.
  • VHH
    Camelids generate functional antibodies lack of light chains, of which the single N-terminal domain is fully capable of antigen binding. These single-domain antibody fragments are named as VHHs, which have a variety of advantages for biotechnological applications.

With our comprehensive structure-based antibody reformatting services, designing and engineering novel antibodies into scFv and VHH is available. We customize the service according to the specific requirements from the customers. We also provide other epitope-specific antibody design services. Please contact us for more information and a detailed quote.

Antibody structure and isotypes. Antibody isotypes. In mammals, antibodies are divided into five isotypes: IgG, IgM, IgA, IgD and IgE, based on the number of Y units and the type of heavy chain. The isotypes differ in their biological properties, functional locations and ability to deal with different antigens: . Most produced Ig.

Describe the structure of antibodies. • They are made up of four chains (two heavy chains and two light chains) which are held together by disulphide bridges. • The constant region is for biological activity while the variable region is for antigen binding. • The variable region is also known as the fragment antigen binding region (Fab


In an experimental setting, Fc and Fab fragments can be generated in the laboratory. The enzyme papain can be used to cleave an immunoglobulin monomer into two Fab fragments and an Fc fragment. Conversely, the enzyme pepsin cleaves below the hinge region, so the result instead is a F(ab')2 fragment and a pFc' fragment. Recently another enzyme for generation of F(ab')2 has been commercially available. The enzyme IdeS (Immunoglobulin degrading enzyme from Streptococcus pyogenes, trade name FabRICATOR) cleaves IgG in a sequence specific manner at neutral pH. The F(ab')2 fragment can be split into two Fab' fragments by mild reduction. [1]

Heavy and light chains, variable and constant regions of an antibody.

An antibody digested by papain yields three fragments: two Fab fragments and one Fc fragment

An antibody digested by pepsin yields two fragments: a F(ab')2 fragment and a pFc' fragment

The variable regions of the heavy and light chains can be fused together to form a single-chain variable fragment (scFv), which is only half the size of the Fab fragment, yet retains the original specificity of the parent immunoglobulin. [2]

Fabs have seen some therapeutic use in emergency medicine as an antidote. Marketed applications include digoxin immune fab and Crofab, a mixture of Fabs for rattlesnake bites. Fabs against colchicine and tricyclic antidepressants has also been produced but are yet to see approval. [3] [4]

Fabs are a common form-factor for monoclonal antibodies designated for therapeutic use. The Fab abciximab, which inhibits blood clotting, works by disabling glycoprotein IIb/IIIa fount on platelets. [5] Ranibizumab, a treatment for macular degeneration, targets vascular endothelial growth factor A, a protein involved in the growth of blood vessels. Certolizumab pegol is a Fab chemically linked to PEG, and it treats various inflammatory disorders by binding away TNFα.

Fab antibodies also have diagnostic use. Arcitumomab is a mouse antibody that recognizes carcinoembryonic antigen, an antigen over-expressed in 95% of colorectal cancers. It is conjugated to a radioactive element, which will label the tumors when viewed with single-photon emission computed tomography. Sulesomab, an antigen that recognizes proteins on the surface of granulocytes, is used to label out infections, again using the 99m Tc isotope. [6]

Fab fragments are often fused to small proteins (<100 kDa) that have lower scattering, resulting in images with less contrast.

  1. ^ Larsson, Lars-Inge (September 1988). Immunocytochemistry: Theory and practice. Crc Press. p. 1. ISBN0-8493-6078-1 .
  2. ^
  3. Janeway, CA, Jr. et al. (2001). Immunobiology (5th ed.). Garland Publishing. ISBN0-8153-3642-X .
  4. ^
  5. Flanagan RJ, Jones AL (2004). "Fab antibody fragments: some applications in clinical toxicology". Drug Saf. 27 (14): 1115–1133. doi:10.2165/00002018-200427140-00004. PMID15554746. S2CID40869324.
  6. ^
  7. Seger D, Kahn S, Krenzelok EP (2005). "Treatment of US crotalidae bites: comparisons of serum and globulin-based polyvalent and antigen-binding fragment antivenins". Toxicol Rev. 24 (4): 217–227. doi:10.2165/00139709-200524040-00002. PMID16499404. S2CID44916236. CS1 maint: multiple names: authors list (link)
  8. ^ Fachinformation Lucentis. Novartis Pharma. Stand 15. November 2007.
  9. ^
  10. W. J. Köstler, C. C. Zielinski (November 2000). "Diagnostische und therapeutische Antikörper in der Onkologie — State of the Art". Acta Chirurgica Austriaca. 32 (6): 260–263.

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Molecular Models: Exploring the Structure of an Antibody

In this activity you will make a paper model of an Immunoglobin G (IgG) antibody, a molecule that plays a critical role in our immune response to pathogens. This antibody molecule has 4 protein chains and 12 domains, so the activity may be best done as a group or class project. Completing parts of the activity as homework may facilitate assembling the antibody in class in a timely manner, which can be followed by discussions.

To learn further details about the structure and function of this molecule, you can compare the paper model to an atomic model of antibody displayed in the online interactive views included here.

The activity is presented in 3 sections:

    - Introduction and some interesting facts - Template and instructions for making the paper model - Interactive display of the atomic structure of an antibody and details about how its structure relates to its function

1. About Antibodies

Antibodies are proteins that recognize and bind to foreign objects in our body. They play a central role in the immune system, by finding pathogens, such as viruses and bacteria, and targeting them for destruction. Antibodies have a distinctive Y-shape, and are composed of two heavy chains and two light chains. The antigen-binding sites are located at the tips of the two arms formed by heavy and light chain domains. For an introduction to the structure and functions of IgG, see the Molecule of the Month features on Antibodies.

In addition to IgG, humans and other mammals produce other types of antibodies, such as the IgM, IgA, IgD and IgE. The heavy chains of all these immunoglobulin molecules vary, leading to differences in the overall shape of the molecule. B-cells recognize invaders through interactions with specialized antibodies on their cell surface (IgM and IgD), and are activated to produce lots of soluble immunoglobulins (IgG) to fight the infection. IgA is secreted in the gut and respiratory tract, helping protect us from any infections there. Finally IgE is secreted by mast cells and is involved in allergies.

The N-terminal domains of immunoglobulin heavy and light chains are variable - i.e. different in different antibodies. Antigens bind to specific pockets at the tips of these variable domains and interact with 6 loops (3 loops each from the heavy and light chains). These loops, called hypervariable loops, are responsible for the complementarity of the antigen-antibody interactions. Hence these hypervariable loops are also called complementarity determining regions (CDR). Subtle and/or major changes in these hypervariable loops of antibodies enables highly specific antigen-antibody interactions. The rest of the domains in the immunoglobulin chains are relatively conserved or constant.

Limited digestion with the protease, papain, chops the antibody into three fragments. Two identical fragments retain the antigen-binding activity and are called Fab fragments, for "Fragment antigen binding." The third fragment has no antigen-binding activity, but was found to crystallize readily, so is named the Fc fragment for "Fragment crystallizable." A number of polysaccharides are covalently linked to this region, providing it some order and rigidity. This fragment interacts with effector molecules and cells by binding to a cellular receptor called the Fc receptor.

Use in Research and Medicine:

Specificity of antigen antibody binding forms the basis for diagnostic tests for many infectious, inflammatory, and immune system diseases. To diagnose a disease, the presence of a specific antigen or antibody is recognized (for example in a blood or mucosa sample) by interacting it with its counterpart antibody or antigen, respectively. In some cases the antibody itself is used as a treatment, such as in the case of some specific cancers and rheumatoid arthritis. In these instances it is critical that the antibody that is administered is very pure, specific and only binds to the antigen of choice. These antibodies, called monoclonal antibodies, prevent cross-reaction with any other related proteins, avoiding side effects and complications.

In research too, antibodies play a very important role in localizing and labeling specific proteins/cells, and forming stable complexes that can be studied. Thus, antibodies are key components of the various diagnostics techniques such as Enzyme Linked Immune Sorbent Assay (ELISA), Western blots, immunofluorescence, etc.

Some broadly-neutralizing antibodies isolated from patients infected with viruses such as HIV and influenza are currently being studied to reverse engineer its antigen and ultimately develop new vaccines. To learn more about the structure and functions of antibody-like molecules, see the Molecule of the Month features on Broadly Neutralizing Antibodies.

Immunoglobulin-like Molecules in Nature:

Camels and sharks make simpler immunoglobulins that are composed of a single type of chain, termed "heavy-chain antibodies" since they do not have a light chain. As with IgG, two chains associate together to form a Y-shaped complex, with several domains forming the constant region in the stem, and a single variable domain forming the antigen-binding site on the arms. Nanobodies, also known as single-domain antibodies, are now engineered from this variable domain. They are much simpler to synthesize than typical two-chain Fab molecules, and are widely used in research and medicine.

To learn more about the structure and functions of antibody-like molecules, see the Molecule of the Month features on Nanobodies.

2. Build a Paper Model of an Antibody

Use this PDF to build a paper model of Antibody.

Folding Instructions

Follow the instructions in the slides demonstrating how to build this antibody model.

Observe in the Antibody paper model and Discuss:
  1. Multiple chains:
    • This model has 4 different chains - the light chains are colored in shades of blue, while the heavy chains in shades of red, orange and pink. As you build the model, can you identify the primary, secondary, tertiary and quaternary structures of the Antibody molecule?
  2. Disulfide bridges:
    • Each immunoglobulin domain has a disulfide bridge. When making the paper model notice how flexible the structure of each domain is, before and after attaching the disulfide link strip. What does this tell you about the function of the disulfide bridges?
    • Disulfide bonds are formed as a result of an oxidation reaction. In which cellular compartment do you think disulfide linkages of the immunoglobulin are formed? (Hint: It is not in the cytoplasm.)

Model limitations

  1. Overall the antibody paper model is quite flexible, even though each of the immunoglobulin domains, and the papain digested fragments (Fab and Fc) regions are well ordered. While the paper model's flexibility at the hinges is representative of the actual antibody structure, covalently linked sugars in the conserved, Fc region make it a little more rigid. The paper model does not include any linked sugars.

3. Explore the Atomic Structure of Antibody (IgG)

The atomic structure of antibody IgG can be visualized using coordinates from the Protein Data Bank. Here the structure from PDB entry 1igt is shown in a JSmol interactive view.

In the JSmol default view the chains are colored similarly to the paper model. Two heavy and two light chains of antibody IgG are linked together by disulfide bonds (sulfur in yellow) to form a "Y-shaped" molecule. Both heavy and light chains of IgG have a repeated domain structure, aptly called the immunoglobulin domain or beta-sandwich, with 3-4 strands on one side and 4-5 strands on the other. This domain structure is often reused by nature in various other immune system molecules and receptors. Notice that a single disulfide bond stabilizes each of the immunoglobulin domains.

The antigen binding sites are on the tips of the two arms, surrounded by the six hypervariable loops. Use the button to color these loops green. You can also highlight the domain structure in the JSmol using the button to color the Fab pink and Fc green. The polysaccharides attached to the immunoglobulin are shown with atomic spheres in the JSmol.

While the overall structure of the many immunoglobulin domains are similar, closer examination of the IgG structure reveals that variable domains (that bind to the antigen) have additional strands and loops and are slightly different from the constant domains (that do not bind the antigen). Use the lower button on the JSmol to display a closeup of only one light chain. Notice that the variable domain (brighter colors in the model coloring scheme, or with green hypervariable loops in the coloring scheme that highlights them) has 4 and 5 beta strands in each sheet forming the beta-sandwich, but the constant domain has 4 and 3 strands.

As the name implies, the hypervariable loops are quite different when you compare different antibodies. The second JSmol compares two antibody Fab fragments--the one from the antibody shown above and one from a broadly-neutralizing antibody that is effective against HIV. The anti-HIV antibody was found to have an extra long loop when compared to other antibodies. Can you suggest a reason why this long loop provides an advantage?

Topics for further exploration

  1. How are antibodies made for use in research and medicine?
  2. How are monoclonal antibodies made?

References: (check formatting of refs).

  1. The structure of a typical antibody molecule from Immunobiology: The Immune System in Health and Disease. 5th edition. (
  2. Refined Structure of an Intact IgG2a Monoclonal Antibody, Biochemistry1997, 36, 1581-1597
  3. Nanobodies: Natural Single-Domain Antibodies Annu. Rev. Biochem. 2013. 82:775-97
  4. Broadly neutralizing antibodies against HIV-1: templates for a vaccine. Virology. 2013 Jan 5 435(1):46-56. doi: 10.1016/j.virol.2012.10.004.

About PDB-101

PDB-101 helps teachers, students, and the general public explore the 3D world of proteins and nucleic acids. Learning about their diverse shapes and functions helps to understand all aspects of biomedicine and agriculture, from protein synthesis to health and disease to biological energy.

Why PDB-101? Researchers around the globe make these 3D structures freely available at the Protein Data Bank (PDB) archive. PDB-101 builds introductory materials to help beginners get started in the subject ("101", as in an entry level course) as well as resources for extended learning.


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