User:Thomas McNamara/Sandbox 1
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Each Immunoglobulin G protein is made of four separate peptide chains --<scene name='80/803917/Immunoglobulin_g/1'> two identical longer chains, called heavy chains, and two identical smaller chains, called light chains.</scene> Together, these four chains come together to form a Y-shaped molecule, with the two binding sites forming at the end of each arm. At a more in-depth look, one can see that each light chain consists of two domains, a variable region and a constant region; while each heavy chain consists of 4 domains, one variable region and three constant regions. Structurally, each domain of each peptide is made up of <scene name='80/803917/Individual_domain_structure/1'>two beta-sheets, pinned together by a disulfide bridge in the middle</scene>. While the disulfide bond provides extra stability, the hydrophobic effect is the driving force behind this structural conformation, with the side chains of each hydrophobic amino acid oriented towards to middle of the 'beta-sheet sandwich.' Additionally, in the constant domains, hydrophilic amino acids orient their side chains outwards so that they can interact with other molecules, such as immune receptors that facilitate the next step in the pathogen degradation pathway. This also hints at the need for each constant domain to retain its amino acid sequence between each Immunoglobulin G protein, as all of these proteins must still bind to immune receptors, despite the pathogen bound. | Each Immunoglobulin G protein is made of four separate peptide chains --<scene name='80/803917/Immunoglobulin_g/1'> two identical longer chains, called heavy chains, and two identical smaller chains, called light chains.</scene> Together, these four chains come together to form a Y-shaped molecule, with the two binding sites forming at the end of each arm. At a more in-depth look, one can see that each light chain consists of two domains, a variable region and a constant region; while each heavy chain consists of 4 domains, one variable region and three constant regions. Structurally, each domain of each peptide is made up of <scene name='80/803917/Individual_domain_structure/1'>two beta-sheets, pinned together by a disulfide bridge in the middle</scene>. While the disulfide bond provides extra stability, the hydrophobic effect is the driving force behind this structural conformation, with the side chains of each hydrophobic amino acid oriented towards to middle of the 'beta-sheet sandwich.' Additionally, in the constant domains, hydrophilic amino acids orient their side chains outwards so that they can interact with other molecules, such as immune receptors that facilitate the next step in the pathogen degradation pathway. This also hints at the need for each constant domain to retain its amino acid sequence between each Immunoglobulin G protein, as all of these proteins must still bind to immune receptors, despite the pathogen bound. | ||
| - | Notably, the two <scene name='80/803917/Individual_domain_structure/4'>antigen binding pockets are formed at the interface between the light and heavy chains' variable domains</scene>. Within each antibody's variable domain are three loops, referred to as hypervariable regions or complimentary determining regions, that differ in amino acid sequence between each Immunoglobulin G protein. Ultimately, it is the amino acid sequence of each of these loops (and therefore the length and conformation of each loop) and the juxtaposition of the six loops coming together that give each antibody a very unique binding pocket. The largest of the three loops, often referred to as H3, is located at the center of the antigen binding site, blocking access in the unliganded form. | + | Notably, the two <scene name='80/803917/Individual_domain_structure/4'>antigen binding pockets are formed at the interface between the light and heavy chains' variable domains</scene>. Within each antibody's variable domain are three loops, referred to as hypervariable regions or complimentary determining regions, that differ in amino acid sequence between each Immunoglobulin G protein. Ultimately, <scene name='80/803917/Antigen_binding_site/1'>it is the amino acid sequence of each of these loops (and therefore the length and conformation of each loop) and the juxtaposition of the six loops coming together that give each antibody a very unique binding pocket</scene>. The largest of the three loops, often referred to as H3, is located at the center of the antigen binding site, blocking access in the unliganded form. |
==References== | ==References== | ||
Current revision
Contents |
Immunoglobulin G
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Immunoglobulin G proteins, more commonly referred to as antibodies, make up a large family of secreted proteins that are potent regulators of the immune system. Furthermore, Immunoglobulin G proteins are the most common type of antibodies present in the serum, and utilize their two identical, but very unique, binding sites to recognize pathogens. It is these binding sites that differ in amino acid sequence between each Immunoglobulin G protein in a particular organism, giving each antibody a different binding target -- ultimately giving the immune system a large class of weapons that can bind to and recognize almost any foreign pathogen.
Function
When a foreign pathogen invades a host organism, it is constantly coming into contact with circulating B-cells. Eventually, one particular B-cell will contain a membrane protein that recognizes and binds to a very specific region on the pathogen, called an epitope. This B-cell will then begin secreting identical Immunoglobulin G proteins whose binding sites recognize only the particular epitope. The secreted antibodies will then circulate throughout the host organism, searching for and binding to any other identical pathogens that display the same epitope. Once bound to the pathogen, the Immunoglobulin G protein can:
1) Neutralize/Immobilize the pathogen, preventing it from functioning; and/or 2) Bind to immune cell receptors that facilitate pathogen degradation.
Disease
Through evolution, organisms have developed antibody-secreting immune systems that do not recognize host proteins/tissues. In rare cases, though, an organism will develop a mutation that leads to their Immunoglobulin G proteins binding to their own cells, causing the host's immune system to attack the host's healthy cells/tissues. This problem is the root of many common auto-immune diseases prevalent today.
Relevance
The key feature of each Immunoglobulin G is its ability to recognize and bind to one very specific epitope. This binding specificity has given antibodies a wide range of applications in both medical and research settings, such as:
1) Identifying if a certain biomarker is present in a patient sample; 2) Neutralizing a mutated protein in patients; 3) Western blots, ELISAs, flow cytometry assays, and more.
Structural highlights
Each Immunoglobulin G protein is made of four separate peptide chains -- Together, these four chains come together to form a Y-shaped molecule, with the two binding sites forming at the end of each arm. At a more in-depth look, one can see that each light chain consists of two domains, a variable region and a constant region; while each heavy chain consists of 4 domains, one variable region and three constant regions. Structurally, each domain of each peptide is made up of . While the disulfide bond provides extra stability, the hydrophobic effect is the driving force behind this structural conformation, with the side chains of each hydrophobic amino acid oriented towards to middle of the 'beta-sheet sandwich.' Additionally, in the constant domains, hydrophilic amino acids orient their side chains outwards so that they can interact with other molecules, such as immune receptors that facilitate the next step in the pathogen degradation pathway. This also hints at the need for each constant domain to retain its amino acid sequence between each Immunoglobulin G protein, as all of these proteins must still bind to immune receptors, despite the pathogen bound.
Notably, the two . Within each antibody's variable domain are three loops, referred to as hypervariable regions or complimentary determining regions, that differ in amino acid sequence between each Immunoglobulin G protein. Ultimately, . The largest of the three loops, often referred to as H3, is located at the center of the antigen binding site, blocking access in the unliganded form.
References
Harris, L. J., Larson, S. B., Hasel, K. W., and McPherson, A. (1997) Refined Structure of an Intact IgG2a Monoclonal Antibody,. Biochemistry. 36, 1581–1597
Stanfield, R. L., Takimoto-Kamimura, M., Rini, J. M., Profy, A. T., and Wilson, I. A. (1993) Major antigen-induced domain rearrangements in an antibody. Structure. 10.1016/0969-2126(93)90024-B
Paul, W. (2013) Fundamental Immunology. 7, 129-149
