Rebecca Martin/Sandbox1: Difference between revisions
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== | == 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='1r70' size='300' frame='true' align='right' caption='monomeric IgA2' /> <applet load='1iga' size='300' frame='true' align='right' caption='monomeric IgA1' /> | ||
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== Dimeric IgA and the J chain== | |||
== Secretory IgA and the Secretory Component == | |||
== Secretory Component == | |||
<applet load='2ocw' size='150' frame='true' align='right' caption='secretory component.' /> | <applet load='2ocw' size='150' frame='true' align='right' caption='secretory component.' /> | ||
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== Insights into Function == | == Insights into Function == | ||
== | == Implications in Science and Medicine == | ||
== | == Evolution and Related Links == | ||
== Limitations of the Current Studies == | == 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 == | == 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 .... | : 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 | |||
Revision as of 07:47, 23 April 2009
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 [2]. The body produces more IgA than any other antibody isotype [3]. In fact, IgA is the most abundant antibody in the body, further illustrating IgA's critical role in immunity [4].
Unlike other antibody isotypes, IgA exists in mutiple oligomeric states [3]. The most common of which are the monomeric, dimeric, and secretory forms [4]. 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 [5]. In the serum, about 90% of the IgA is monomeric IgA1 [4], phaocytosis, and eosinophil degranulation. Binding to the pIgR results in transoocytosis and IgA secretion [2]. Exploring IgA's structure and protein interactions illuminates the unique and critical function IgA plays in humoral immunity.
Antibody Structure and the Immunoglobulin DomainAntibody 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
- Forms of IgA
Dimeric Structure
|
- Secretory Component
Monomeric IgAMonomeric 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
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|
|
|
Dimeric IgA and the J chainDimeric IgA and the J chain
Secretory IgA and the Secretory ComponentSecretory IgA and the Secretory Component
|
Insights into FunctionInsights into Function
Implications in Science and MedicineImplications in Science and Medicine
Evolution and Related LinksEvolution and Related Links
Limitations of the Current StudiesLimitations 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 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 ....
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
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
- ↑ 2.0 2.1 2.2 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
- ↑ 3.0 3.1 3.2 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
- ↑ 4.0 4.1 4.2 Boehm MK, Woof JM, Kerr MA, Perkins SJ. The Fab and Fc fragments of IgA1 exhibit a different arrangement from that in IgG: a study by X-ray and neutron solution scattering and homology modelling. J Mol Biol. 1999 Mar 12;286(5):1421-47. PMID:10064707 doi:http://dx.doi.org/10.1006/jmbi.1998.2556
- ↑ Bonner A, Almogren A, Furtado PB, Kerr MA, Perkins SJ. The nonplanar secretory IgA2 and near planar secretory IgA1 solution structures rationalize their different mucosal immune responses. J Biol Chem. 2009 Feb 20;284(8):5077-87. Epub 2008 Dec 23. PMID:19109255 doi:http://dx.doi.org/10.1074/jbc.M807529200