Rebecca Martin/Sandbox1
Introduction to IgAIntroduction to IgA
Template:STRUCTURE 1iga
The most extensive surface in contact with the external environment is not our skin, but the epithelial lining of our gastrointestinal, respiratory, and urogenital tracts [1]. As a first line of defense in maintainance the integrity our mucosa, the immune system manufatures and secretes dimeric IgA to neutralize pathogenic organisms [2] and exclude the entry of commensals at the mucosal border [3]. In the serum, IgA functions as a second line of defense against pathogens that may breech the epithelial boundary Cite error: Invalid parameter in <ref> tag. 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, the a monomeric, a dimeric, and secretory forms being most common <ref name="ten" /ref>,<ref name="nineseven" /ref>. 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 burst, phaocytosis, and eosinophil degranulation. Binding to the pIgR results in transoocytosis and IgA secretion <ref name="five" /ref>. At the mucosal 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" /ref>. In the serum, about 90% of the IgA is monomeric IgA1 <ref name ="ten" /ref>.
StructureStructure
- Immunoglobulin Structure
Antibodies are composed of a heavy chain and a light chain.
Fab fragment
- Forms of IgA
Dimeric Structure
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- Secretory Component
IgA1 and IgA2IgA1 and IgA2
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Secretory ComponentSecretory Component
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Insights into FunctionInsights into Function
EvolutionEvolution
Implications in Science and MedicineImplications in Science and Medicine
Limitations of the Current StudiesLimitations of the Current Studies
- Because of the nature of the IgA molecule, crystalizing this structure was not possible. Therefore, many of these structures are based on models and not actual crystal structures. Because ...., the models were depositable in the PDB. I tried to include other crystallographic data when available, supporting the proposed models- as the authors did in the original papers.
Questions for the FutureQuestions 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 ....
LinksLinks
IgAIgA
- Monomeric
- 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 and2imn
- Dimeric and Secretory
ReceptorsReceptors
- 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)Other Isotypes (for comparison)
- IgM: Solution structure of human Immunoglobulin M 2rcj
- IgG:
- IgD:
- IgE:
ReferencesReferences
- ↑ Bonner A, Perrier C, Corthesy B, Perkins SJ. Solution structure of human secretory component and implications for biological function. J Biol Chem. 2007 Jun 8;282(23):16969-80. Epub 2007 Apr 11. PMID:17428798 doi:http://dx.doi.org/10.1074/jbc.M701281200
- ↑ Furtado PB, Whitty PW, Robertson A, Eaton JT, Almogren A, Kerr MA, Woof JM, Perkins SJ. Solution structure determination of monomeric human IgA2 by X-ray and neutron scattering, analytical ultracentrifugation and constrained modelling: a comparison with monomeric human IgA1. J Mol Biol. 2004 May 14;338(5):921-41. PMID:15111057 doi:http://dx.doi.org/10.1016/j.jmb.2004.03.007
- ↑ Bonner A, Almogren A, Furtado PB, Kerr MA, Perkins SJ. Location of secretory component on the Fc edge of dimeric IgA1 reveals insight into the role of secretory IgA1 in mucosal immunity. Mucosal Immunol. 2009 Jan;2(1):74-84. Epub 2008 Oct 8. PMID:19079336 doi:http://dx.doi.org/10.1038/mi.2008.68