Rebecca martin/sandbox2: Difference between revisions
New page: == Introduction to IgA == {{STRUCTURE_1iga | PDB=1iga | SCENE= }} The most extensive surface in contact with the external environment is not our skin, but the epithelial lining of our ... |
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Unlike other antibody isotypes, IgA exists in mutiple oligomeric states <ref name="nineseven" />. The most common of which are the monomeric, dimeric, and secretory forms <ref name="ten" />. At least two isotypes exist, termed IgA1 and IgA2. IgA2 can further be categorized into 2 allotypes: IgA2 m(1) and IgA2 m(2). The receptors for IgA include the Fcα Receptor (FcαRI; CD89) and the polyimmunologlobulin receptor (pIgRI). When binding to FcαRI results in the dimerization, the consequent signaling results in effector functions, including respiratory burstmucosal surface, an approximately equal ratio of secretory IgA1 (sIgA1) to secretory IgA2 (sIgA2) reside at the mucosal surface, with the exception of the colon, where the majority is sIgA2 <ref name="nineten" />. In the serum, about 90% of the IgA is monomeric IgA1 <ref name ="ten" />, phaocytosis, and eosinophil degranulation. Binding to the pIgR results in transoocytosis and IgA secretion <ref name="five" />. Exploring IgA's structure and protein interactions illuminates the unique and critical function IgA plays in humoral immunity. | Unlike other antibody isotypes, IgA exists in mutiple oligomeric states <ref name="nineseven" />. The most common of which are the monomeric, dimeric, and secretory forms <ref name="ten" />. At least two isotypes exist, termed IgA1 and IgA2. IgA2 can further be categorized into 2 allotypes: IgA2 m(1) and IgA2 m(2). The receptors for IgA include the Fcα Receptor (FcαRI; CD89) and the polyimmunologlobulin receptor (pIgRI). When binding to FcαRI results in the dimerization, the consequent signaling results in effector functions, including respiratory burstmucosal surface, an approximately equal ratio of secretory IgA1 (sIgA1) to secretory IgA2 (sIgA2) reside at the mucosal surface, with the exception of the colon, where the majority is sIgA2 <ref name="nineten">PMID:19109255 </ref>. In the serum, about 90% of the IgA is monomeric IgA1 <ref name ="ten" />, phaocytosis, and eosinophil degranulation. Binding to the pIgR results in transoocytosis and IgA secretion <ref name="five" />. Exploring IgA's structure and protein interactions illuminates the unique and critical function IgA plays in humoral immunity. | ||
== Antibody Structure and the Immunoglobulin Domain == | |||
Tetramer of 2 light chains and 2 heavy chains, held together w disulfide bonds and noncovalent interactions | |||
Light chains composed of 2 Ig domains: one V-type and one C-type. Heavy chains composed of 4 Ig domains: one V-type and 3 C-type. | |||
Ig domains | |||
C-type domains | |||
Related structures | |||
V-type | |||
Variable domains determine antigen specificity. The loops @ ___ are the most variable regions, and are known as compliment determining regions | |||
constant regions determine the isotype: IgA, IgD, IgM, IgG, or IgE | |||
* Immunoglobulin Structure | |||
Antibodies are composed of a heavy chain and a light chain. | |||
Fab fragment | |||
<scene name='Rebecca_Martin/Sandbox1/Cdr_side_view/1'>CDR side view</scene> | |||
<scene name='Rebecca_Martin/Sandbox1/Cdr_top_view/1'>CDR top view</scene> | |||
<scene name='Rebecca_Martin/Sandbox1/Cdr_360_view/1'>CDR with Ag</scene> | |||
* Forms of IgA | |||
Dimeric Structure | |||
<applet load='2qtj' size='300' frame='true' align='right' caption=dimeric IgA1' /> | |||
<scene name='Rebecca_Martin/Sandbox1/Dimeric_iga_1/1'>dimeric iga</scene> | |||
* Secretory Component | |||
== Monomeric IgA == | |||
Monomeric iga: 12 domains ~ IgG 10064707 | |||
2 light, 2 heavy. 10064707 | |||
2 domains in Light = vl and cl. 10064707 | |||
4 domains in heavy. Heavy = vh, c1, c2, c3 10064707 | |||
Gen structure of domains = beta sheet sandwhich structure 10064707 + a conserved disulphide bond 15111057 | |||
Beta strands = A to G 10064707 | |||
V domains = 9 strands (DEBA-GFCC’C’’) 10064707 | |||
C domains = 7 or 8 strands DEBA-GFC(C’) 10064707 | |||
Disulfide Cys 311-Cys 471 10064707 | |||
90% monomeric IgA1) 10064707 | |||
<applet load='1r70' size='300' frame='true' align='right' caption='monomeric IgA2' /> <applet load='1iga' size='300' frame='true' align='right' caption='monomeric IgA1' /> | |||
<applet load='3cm9' size='250' frame='true' align='left' caption=secretory IgA2' /> <applet load='3chn' size='250' frame='true' align='left' caption='secretory IgA1' /> | |||
== Dimeric IgA and the J chain== | |||
== Secretory IgA and the Secretory Component == | |||
<applet load='2ocw' size='150' frame='true' align='right' caption='secretory component.' /> | |||
== Insights into Function == | |||
== Implications in Science and Medicine == | |||
== Evolution and Related Links == | |||
== Limitations of the Current Studies == | |||
: 10064707; 15111057 xray and neutron scattering analysis + analytical ultracentrifugation and analyzed w constrained modeling 2/2 high carb and flex = difficult to crystalize 18178841 | |||
== Questions for the Future == | |||
: Because of the limitating resolution of these models, many details concerning the binding residues and residue interactions are left unknown. Crystallographic structure will yield further insights into the structure of IgA, the interactions between IgA and other molecules, and .... | |||
SC aa interact w J chain? CDR-like motifs @ D1 binds ? @ IgA; Does SC open upon binding?; stoichiometry of binding? Locations of oligos on SC? Differences in binding IgA1 vs IgA2 17428798 | |||
Binding motifs SC and IgA1 18178841 | |||
Structure of IgA involved in IgA nephropathy 18178841 | |||
== Links == | |||
=== IgA === | |||
* Monomeric | |||
:: Model of human IgA1 determined by solution scattering, curve-fitting, and homology modeling [[1iga]] | |||
:: Model of human IgA2 determined by solution scattering, curve fitting and homology modelling [[1r70]] | |||
* Fab and Fc Fragments | |||
:: Refined crystal structure of the galactan-binding immunoglobulin fab j539 at 1.95-angstroms resolution [[2fbj]] | |||
:: Phosphocholine binding immunoglobulin fab mc/pc603. an x-ray diffraction study at 2.7 angstroms [[1mcp]] | |||
:: Phosphocholine binding immunoglobulin fab mc/pc603. an x-ray diffraction study at 3.1 angstroms [[2mcp]] | |||
:: Crystal structure of human FcaRI bound to IgA1-Fc [[1ow0]] | |||
::Refined crystal structure of a recombinant immunoglobulin domain and a complementarity-determining region 1-grafted mutant [[2imm]] and[[2imn]] | |||
* Dimeric and Secretory | |||
:: Solution structure of human dimeric immunoglobulin A [[2qtj]] | |||
:: Solution structure of human secretory IgA1 [[3chn]] | |||
:: Solution Structure of Human SIgA2 [[3cm9]] | |||
:: Solution structure of human secretory component [[2ocw]] | |||
=== Receptors === | |||
* Crystal Structure of a Ligand-Binding Domain of the Human Polymeric Ig Receptor, pIgR [[1XED]] | |||
* Crystal structure of human FcaRI [[10vz]] | |||
* Crystal structure of a Staphylococcus aureus protein (SSL7) in complex with Fc of human IgA1 [[2qej]] | |||
=== Other Isotypes (for comparison) === | |||
* IgM: Solution structure of human Immunoglobulin M [[2rcj]] | |||
* IgG: | |||
* IgD: | |||
* IgE: | |||
== References == | |||
<references /> | |||