IgA - Revision history

Michal Harel at 09:23, 11 July 2013

Michal Harel — Thu, 11 Jul 2013 09:23:59 GMT

←Older revision		Revision as of 09:23, 11 July 2013
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-		+	<StructureSection load='1iga' size='450' side='right' scene='' caption='Model of human Iga1 [[1iga]]'>
-	<StructureSection load='1iga' size='450' side='right' scene='' caption=''>	+

	== Introduction to IgA ==		== Introduction to IgA ==

Michal Harel at 09:21, 11 July 2013

Michal Harel — Thu, 11 Jul 2013 09:21:35 GMT

←Older revision		Revision as of 09:21, 11 July 2013
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-	{{STRUCTURE_1iga\| PDB=1iga \| SIZE=400\| SCENE= \|right\|CAPTION=Human calcineurin subunit β (yellow and green) and calmodulin-dependent calcineurin subunit α (grey and pink) complex with polypeptide (magenta), phosphate, Ca+2 (green), Fe +3 and Zn+2 (grey) ions, [[1iga]] }}	+
	<StructureSection load='1iga' size='450' side='right' scene='' caption=''>		<StructureSection load='1iga' size='450' side='right' scene='' caption=''>

Michal Harel at 09:20, 11 July 2013

Michal Harel — Thu, 11 Jul 2013 09:20:50 GMT

←Older revision		Revision as of 09:20, 11 July 2013
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		+	{{STRUCTURE_1iga\| PDB=1iga \| SIZE=400\| SCENE= \|right\|CAPTION=Human calcineurin subunit β (yellow and green) and calmodulin-dependent calcineurin subunit α (grey and pink) complex with polypeptide (magenta), phosphate, Ca+2 (green), Fe +3 and Zn+2 (grey) ions, [[1iga]] }}
	<StructureSection load='1iga' size='450' side='right' scene='' caption=''>		<StructureSection load='1iga' size='450' side='right' scene='' caption=''>
		+
	== Introduction to IgA ==		== Introduction to IgA ==
	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 <ref name="seven">PMID:17428798</ref>. As a first line of defense in maintenance the integrity our mucosa, the immune system manufactures and secretes dimeric IgA to neutralize pathogenic organisms <ref name="five">PMID:15111057</ref> and exclude the entry of commensals at the mucosal border <ref name="nineseven">PMID:19079336</ref>. In the serum, IgA functions as a second line of defense against pathogens that may breech the epithelial boundary <ref name="five" />. The body produces more IgA than any other antibody isotype <ref name="nineseven"/>. In fact, IgA is the most abundant antibody in the body, further illustrating IgA's critical role in immunity <ref name="ten">PMID:10064707</ref>.		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 <ref name="seven">PMID:17428798</ref>. As a first line of defense in maintenance the integrity our mucosa, the immune system manufactures and secretes dimeric IgA to neutralize pathogenic organisms <ref name="five">PMID:15111057</ref> and exclude the entry of commensals at the mucosal border <ref name="nineseven">PMID:19079336</ref>. In the serum, IgA functions as a second line of defense against pathogens that may breech the epithelial boundary <ref name="five" />. The body produces more IgA than any other antibody isotype <ref name="nineseven"/>. In fact, IgA is the most abundant antibody in the body, further illustrating IgA's critical role in immunity <ref name="ten">PMID:10064707</ref>.

Alexander Berchansky at 13:34, 20 March 2013

Alexander Berchansky — Wed, 20 Mar 2013 13:34:32 GMT

←Older revision		Revision as of 13:34, 20 March 2013
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	'''Fab and Fc fragments'''		'''Fab and Fc fragments'''
-	:Another common way of describing antibody structure is in terms of its Fab and Fc fragments. Each light chains are composed of 2 immunoglobulin domains: one variable domain~~</scene>~~ and one constant domain. Heavy chains composed of 4 Ig domains: one V-type and 3 C-type, named CH1 - CH3. A linking hinge region separates the CH2 and CH3 domains. Proteolytic cleavage at the hinge region by the protease papain, or a similar protease, yields 2 Fab fragments and 1 Fc fragment. Each <scene name='Rebecca_Martin/Sandbox1/Fab_ex/1'>Fab fragment</scene> contains 2 variable domains, one from the heavy chain and one from the light chain, and 2 constant domains one from the light chain and the Ch1 domain from the heavy chain. The <scene name='Rebecca_Martin/Sandbox1/Fc/1'>Fc fragment</scene> Fc fragment contains 4 constant domains: the Ch2 and Ch3 domains from each of the heavy chains. Since the variable portions determine antigen specificity, the Fab fragments are generally thought of as the antigen-binding portion. The Fc fragment is important in binding various receptors, many of which are isotype specific and are named after the isotype of the ligand, i.e. FcαR binds the Fc portion of IgA.	+	:Another common way of describing antibody structure is in terms of its Fab and Fc fragments. Each light chains are composed of 2 immunoglobulin domains: one variable domain and one constant domain. Heavy chains composed of 4 Ig domains: one V-type and 3 C-type, named CH1 - CH3. A linking hinge region separates the CH2 and CH3 domains. Proteolytic cleavage at the hinge region by the protease papain, or a similar protease, yields 2 Fab fragments and 1 Fc fragment. Each <scene name='Rebecca_Martin/Sandbox1/Fab_ex/1'>Fab fragment</scene> contains 2 variable domains, one from the heavy chain and one from the light chain, and 2 constant domains one from the light chain and the Ch1 domain from the heavy chain. The <scene name='Rebecca_Martin/Sandbox1/Fc/1'>Fc fragment</scene> Fc fragment contains 4 constant domains: the Ch2 and Ch3 domains from each of the heavy chains. Since the variable portions determine antigen specificity, the Fab fragments are generally thought of as the antigen-binding portion. The Fc fragment is important in binding various receptors, many of which are isotype specific and are named after the isotype of the ligand, i.e. FcαR binds the Fc portion of IgA.

	'''Immunoglobulin domains'''		'''Immunoglobulin domains'''

Alexander Berchansky at 13:30, 20 March 2013

Alexander Berchansky — Wed, 20 Mar 2013 13:30:23 GMT

←Older revision		Revision as of 13:30, 20 March 2013
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	:Crystallographic structure will yield further insights into the structure of IgA, the interactions between IgA and other molecules.		:Crystallographic structure will yield further insights into the structure of IgA, the interactions between IgA and other molecules.

-		+	</StructureSection>
-		+	__NOTOC__
	== Links ==		== Links ==
	=== IgA ===		=== IgA ===

Alexander Berchansky at 13:28, 20 March 2013

Alexander Berchansky — Wed, 20 Mar 2013 13:28:45 GMT

←Older revision		Revision as of 13:28, 20 March 2013
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	:These data must be taken into account with other hinge region characteristics <ref name="five"/>. IgA1’s hinge region contains 5 sites of O-glycosylation, while IgA2’s hinge region contains none. In addition, IgA1’s hinge region contains 10 Pro residues, while IgA2’s region contains 6. In comparison, IgG’s hinge region contains No glycine residues reside in the hinge regions of either IgA1 or IgA2. The presence of prolines, the absence of glycine and the presence of glycosylated residues in IgA1 all amount to '''increased hinge rigidity''' in comparison to IgG1.		:These data must be taken into account with other hinge region characteristics <ref name="five"/>. IgA1’s hinge region contains 5 sites of O-glycosylation, while IgA2’s hinge region contains none. In addition, IgA1’s hinge region contains 10 Pro residues, while IgA2’s region contains 6. In comparison, IgG’s hinge region contains No glycine residues reside in the hinge regions of either IgA1 or IgA2. The presence of prolines, the absence of glycine and the presence of glycosylated residues in IgA1 all amount to '''increased hinge rigidity''' in comparison to IgG1.
-	~~[[Image:Disulfide_glycos.jpg\|thumb\|Adapted from Furtado, et al 2004.]]~~	+
	'''N-glycosylation'''		'''N-glycosylation'''
	:In the harsh mucosal environment, glycosylated residues protect the protein from proteases <ref name="five"/>. Both IgA1 and IgA2 display N-glycosylated residues. IgA1 has 3, at N263 on beta strand B on the Ch2 chain and on the J tail at N459. In IgA2, additional sites of N-glycosylation include Asn166 on the beta strand G of Ch1 and Asn337 of beta strand G on Ch2. Some alloforms of IgA2 are also N-glycosylated at Asn211 on Ch2. An increased need for protection against proteolytic cleavage at the hinge region accounts for the presence of O-glycosylation in IgA1’s hinge region, particularly cleavage by bacterial metalloproteases. The glycosylation residues provide increased steric hindrance, and creating difficulty in fitting the peptide in the protease’s active site. In comparison to IgG, which is only 2.9% (w/w) glycosylated, IgA1 is 9.5% (w/w) and IgA2 is 11% (w/w) glycosylated. Overall, IgA1 is more susceptible to proteases than IgA2.		:In the harsh mucosal environment, glycosylated residues protect the protein from proteases <ref name="five"/>. Both IgA1 and IgA2 display N-glycosylated residues. IgA1 has 3, at N263 on beta strand B on the Ch2 chain and on the J tail at N459. In IgA2, additional sites of N-glycosylation include Asn166 on the beta strand G of Ch1 and Asn337 of beta strand G on Ch2. Some alloforms of IgA2 are also N-glycosylated at Asn211 on Ch2. An increased need for protection against proteolytic cleavage at the hinge region accounts for the presence of O-glycosylation in IgA1’s hinge region, particularly cleavage by bacterial metalloproteases. The glycosylation residues provide increased steric hindrance, and creating difficulty in fitting the peptide in the protease’s active site. In comparison to IgG, which is only 2.9% (w/w) glycosylated, IgA1 is 9.5% (w/w) and IgA2 is 11% (w/w) glycosylated. Overall, IgA1 is more susceptible to proteases than IgA2.
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	==sIgA1 and sIgA2==		==sIgA1 and sIgA2==
-	[[Image:SIgA.jpg\|thumb\|Adapted from Bonner, et al 2009 and Bonner, et al 2008.]]
	:Binding of the secretory component to the convex edge of the Fc region of dimeric IgA1 maintains <scene name='Rebecca_Martin/Sandbox1/Siga1def/1'>Secretory IgA1</scene> in a near planar conformation, <ref name="nineten" />, <ref name="eight" />. The Fc regions align end to end without overlap, and the fab fragments remain in alignment with the Fc plane. In contrast, <scene name='Rebecca_Martin/Sandbox1/Siga1/1'>Secretory IgA2</scene> fab fragments remain out of alignment with the Fc plane. Because the secretory component resides at the convex region of the Fc portion, the D1 and D5 impart steric hindrance on the fab fragments, which are forced out of alignment. Consequently, IgA2 assumes a nonplanar conformation. The longer hinge region of IgA1 allows it to maintain its planar conformation.		:Binding of the secretory component to the convex edge of the Fc region of dimeric IgA1 maintains <scene name='Rebecca_Martin/Sandbox1/Siga1def/1'>Secretory IgA1</scene> in a near planar conformation, <ref name="nineten" />, <ref name="eight" />. The Fc regions align end to end without overlap, and the fab fragments remain in alignment with the Fc plane. In contrast, <scene name='Rebecca_Martin/Sandbox1/Siga1/1'>Secretory IgA2</scene> fab fragments remain out of alignment with the Fc plane. Because the secretory component resides at the convex region of the Fc portion, the D1 and D5 impart steric hindrance on the fab fragments, which are forced out of alignment. Consequently, IgA2 assumes a nonplanar conformation. The longer hinge region of IgA1 allows it to maintain its planar conformation.

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	== Implications in Medicine and Science ==		== Implications in Medicine and Science ==
	[[Image:IgA_IFA.jpg\|thumb\|Immunofluorescence detecting IgA in IgA glomerulonephritis. From http://www.unckidneycenter.org/images/IgA_IFA.jpg, with permission]]		[[Image:IgA_IFA.jpg\|thumb\|Immunofluorescence detecting IgA in IgA glomerulonephritis. From http://www.unckidneycenter.org/images/IgA_IFA.jpg, with permission]]
		+
	:IgA nephropathy is the most prevalent cause of chronic glomerulonephritis in the world and is caused by polymeric IgA1 deposited at the kidney glomeruli <ref name="eight"/>. Notably, 90% of serum IgA is IgA1, mostly in the monomeric form. The observation that individuals with IgA myeloma [http://en.wikipedia.org/wiki/Multiple_myeloma] lack nephropathy suggests an abnormality in IgA structure, leading to an abnormal amount of polymerization. Steric hindrance of the fab segments normally limits the amount of polymerization of IgA. Bonner, et al proposes that a disturbance in the hinge region or an absence of fab. Similarly, decreased O-glycosylation might could destabilize the hinge region, allowing IgA to self associate. Likewise, destabilizing this region might make IgA susceptible to cleavage of fab fragments by bacterial proteases, leading to self aggregation and renal pathology. For more information on IgA nephropathy: [http://http://www.unckidneycenter.org/contact.html]. <ref name="sn">Falk, R. "IgA Nephropathy." UNC Kidney Center, from http://www.unckidneycenter.org/kidneyhealthlibrary/iganephropathy.html.</ref>.		:IgA nephropathy is the most prevalent cause of chronic glomerulonephritis in the world and is caused by polymeric IgA1 deposited at the kidney glomeruli <ref name="eight"/>. Notably, 90% of serum IgA is IgA1, mostly in the monomeric form. The observation that individuals with IgA myeloma [http://en.wikipedia.org/wiki/Multiple_myeloma] lack nephropathy suggests an abnormality in IgA structure, leading to an abnormal amount of polymerization. Steric hindrance of the fab segments normally limits the amount of polymerization of IgA. Bonner, et al proposes that a disturbance in the hinge region or an absence of fab. Similarly, decreased O-glycosylation might could destabilize the hinge region, allowing IgA to self associate. Likewise, destabilizing this region might make IgA susceptible to cleavage of fab fragments by bacterial proteases, leading to self aggregation and renal pathology. For more information on IgA nephropathy: [http://http://www.unckidneycenter.org/contact.html]. <ref name="sn">Falk, R. "IgA Nephropathy." UNC Kidney Center, from http://www.unckidneycenter.org/kidneyhealthlibrary/iganephropathy.html.</ref>.

Alexander Berchansky at 13:26, 20 March 2013

Alexander Berchansky — Wed, 20 Mar 2013 13:26:12 GMT

←Older revision		Revision as of 13:26, 20 March 2013
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	== The J Chain allows IgA to form Dimers==		== The J Chain allows IgA to form Dimers==
-	~~<applet load='2qtj' size='425' frame='true' align='right' caption='dimeric IgA1' />~~	+
	:The IgA structure has an addition 18 kDa, 137 residue polypeptide chain called the <scene name='Rebecca_Martin/Sandbox1/Iga1_dimeric/2'>J chain</scene> <ref name ="ten" />. This 18 kDa, 137-residue polypeptide chain is comprised of 2 immunoglobulin-like domains. The J chain is covalently attached to the C terminal Cys471 on IgA's Ch3 domain <ref name="eight">PMID: 18178841</ref> via a disulfide bridge with either the J chain’s Cys 14 or the Cys 68 <ref name="ten"/>, <ref name="eight"/>. The J chain has a single N-linked oligosaccharide 15111057, which increases rigidity and offers protection against proteases. The J chain allows IgA to form <scene name='Rebecca_Martin/Sandbox1/Iga1_dimeric/1'>dimers</scene>, and less often trimer and tetramers. These polymers are rare because steric hindrance from the T-shaped Fab regions makes polymerization thermodynamically unfavorable.		:The IgA structure has an addition 18 kDa, 137 residue polypeptide chain called the <scene name='Rebecca_Martin/Sandbox1/Iga1_dimeric/2'>J chain</scene> <ref name ="ten" />. This 18 kDa, 137-residue polypeptide chain is comprised of 2 immunoglobulin-like domains. The J chain is covalently attached to the C terminal Cys471 on IgA's Ch3 domain <ref name="eight">PMID: 18178841</ref> via a disulfide bridge with either the J chain’s Cys 14 or the Cys 68 <ref name="ten"/>, <ref name="eight"/>. The J chain has a single N-linked oligosaccharide 15111057, which increases rigidity and offers protection against proteases. The J chain allows IgA to form <scene name='Rebecca_Martin/Sandbox1/Iga1_dimeric/1'>dimers</scene>, and less often trimer and tetramers. These polymers are rare because steric hindrance from the T-shaped Fab regions makes polymerization thermodynamically unfavorable.

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	'''Limiting Effector Responses through Decreased FcαR Binding'''		'''Limiting Effector Responses through Decreased FcαR Binding'''
-	<applet load='1ow0' size='300' frame='true' align='right' caption='Fc portion of IgA bound to FcαR' />
	:The FcαR binding sites are located one per heavy chain at each Ch2-Ch3 interface. Both domains contribute one binding site. So, the stoichiometry between monomeric IgA and the FcαR is <scene name='Rebecca_Martin/Sandbox1/Fc/3'>2:1</scene> <ref name="five"/>. The Fc portion is shown in red, and the receptor is in blue. Dimerization would increase this stoichiometry 4:1; however, 2 of the binding sites will be <scene name='Rebecca_Martin/Sandbox1/Siga1_sites_covered/1'>covered by the secretory component</scene>. Because of <scene name='Rebecca_Martin/Sandbox1/Fc/4'>orientation</scene> constraints, only 1 of the 2 remaining binding sites will be available to bind receptor. Therefore, physiologic stoichiometry is 1:1.		:The FcαR binding sites are located one per heavy chain at each Ch2-Ch3 interface. Both domains contribute one binding site. So, the stoichiometry between monomeric IgA and the FcαR is <scene name='Rebecca_Martin/Sandbox1/Fc/3'>2:1</scene> <ref name="five"/>. The Fc portion is shown in red, and the receptor is in blue. Dimerization would increase this stoichiometry 4:1; however, 2 of the binding sites will be <scene name='Rebecca_Martin/Sandbox1/Siga1_sites_covered/1'>covered by the secretory component</scene>. Because of <scene name='Rebecca_Martin/Sandbox1/Fc/4'>orientation</scene> constraints, only 1 of the 2 remaining binding sites will be available to bind receptor. Therefore, physiologic stoichiometry is 1:1.

Alexander Berchansky at 13:22, 20 March 2013

Alexander Berchansky — Wed, 20 Mar 2013 13:22:23 GMT

←Older revision		Revision as of 13:22, 20 March 2013
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	=== Compare and Contrast ===		=== Compare and Contrast ===
		+	====IgA1====
		+	*<scene name='Rebecca_Martin/Sandbox1/Iga1_overview/1'>IgA1</scene>

-	~~{\| border="1"~~	+	*<scene name='Rebecca_Martin/Sandbox1/Iga1_hinge_ser_thr/1'>Potential Sites of O-linked Glycosylation (5 residues per hinge glycosylated)</scene> Protect from proteases and increase hinge rigidity. Note the extended hinge region of 23 amino acids, extending IgA1's antigenic reach.
-	\|-	+
-	~~! <applet load='1iga' size='200' frame='true' align='right' />~~	+
-	\|<scene name='Rebecca_Martin/Sandbox1/~~Iga1_overview~~/1'>~~IgA1~~</scene>	+

-	<scene name='Rebecca_Martin/Sandbox1/~~Iga1_hinge_ser_thr~~/1'>~~Potential Sites of O-linked Glycosylation (5 residues per hinge glycosylated)~~</scene> ~~Protect from proteases and increase~~ hinge rigidity~~. Note the extended hinge region of 23 amino acids, extending IgA1's antigenic reach~~.	+	*<scene name='Rebecca_Martin/Sandbox1/Iga1_hinge_proline/1'>Hinge Prolines</scene> Increase hinge rigidity.

-	<scene name='Rebecca_Martin/Sandbox1/~~Iga1_hinge_proline~~/1'>~~Hinge Prolines~~</scene> ~~Increase~~ hinge rigidity.	+	*<scene name='Rebecca_Martin/Sandbox1/Iga1_n_glycos/2'>N-glycosylated residues</scene> Protect from proteases and increase hinge rigidity.

-	<scene name='Rebecca_Martin/Sandbox1/~~Iga1_n_glycos~~/2'>~~N-glycosylated residues~~</scene> ~~Protect from proteases and increase hinge rigidity.~~	+	*<scene name='Rebecca_Martin/Sandbox1/Iga1_j_chain/1'>J chain</scene>

-	<scene name='Rebecca_Martin/Sandbox1/~~Iga1_j_chain~~/1'>~~J chain~~</scene>	+	*<scene name='Rebecca_Martin/Sandbox1/Siga1def/1'>Secretory IgA1</scene> planar (fab fragments aligned with Fc portion)

-	<scene name='Rebecca_Martin/Sandbox1/Siga1def/1'>Secretory IgA1</scene> planar (fab fragments aligned with Fc portion)
-	\|-
-	! <applet load='1r70' size='200' frame='true' align='left' />
-	\|<scene name='Rebecca_Martin/Sandbox1/Iga2_spin/1'>IgA2</scene>

-	<scene name='Rebecca_Martin/Sandbox1/~~Iga2_hinge_length~~/1'>~~Hinge length~~</scene> ~~10 amino acids in length~~	+	====IgA2====
		+	*<scene name='Rebecca_Martin/Sandbox1/Iga2_spin/1'>IgA2</scene>

-	<scene name='Rebecca_Martin/Sandbox1/Iga2_hinge_length/1'>Hinge ~~glycosylation~~</scene> ~~Protect from proteases and increase hinge rigidity.~~	+	*<scene name='Rebecca_Martin/Sandbox1/Iga2_hinge_length/1'>Hinge length</scene> 10 amino acids in length

-	<scene name='Rebecca_Martin/Sandbox1/~~Iga2_hinge_proline~~/1'>Hinge ~~Proline~~</scene> ~~Increase~~ hinge rigidity	+	*<scene name='Rebecca_Martin/Sandbox1/Iga2_hinge_length/1'>Hinge glycosylation</scene> Protect from proteases and increase hinge rigidity.

-	<scene name='Rebecca_Martin/Sandbox1/~~Iga2_j_chain~~/1'>~~J chain~~</scene>	+	*<scene name='Rebecca_Martin/Sandbox1/Iga2_hinge_proline/1'>Hinge Proline</scene> Increase hinge rigidity

-	<scene name='Rebecca_Martin/Sandbox1/~~Siga1~~/1'>~~Secretory IgA2~~</scene> ~~nonplanar (fab fragments not aligned with Fc portion)~~	+	*<scene name='Rebecca_Martin/Sandbox1/Iga2_j_chain/1'>J chain</scene>

-	\|-	+	*<scene name='Rebecca_Martin/Sandbox1/Siga1/1'>Secretory IgA2</scene> nonplanar (fab fragments not aligned with Fc portion)
-	~~! <applet load='1r70' size='200' frame='true' align='left' />~~	+
-	\|<scene name='Rebecca_Martin/Sandbox1/~~Igg_y_shape~~/1'>~~IgG~~</scene> ~~Y shaped,~~ with ~~an intermediate length hinge region.~~	+

-	<scene name='Rebecca_Martin/Sandbox1/~~Igg_disulfides~~/1'>IgG~~: disulfide bonds connecting the heavy and light chains~~</scene>	+	====IgG====
		+	*<scene name='Rebecca_Martin/Sandbox1/Igg_y_shape/1'>IgG</scene> Y shaped, with an intermediate length hinge region.

-	<scene name='Rebecca_Martin/Sandbox1/~~Igg_glycines~~/1'>IgG: ~~glycines (black)~~</scene> ~~increase hinge flexibility. There are no proline residues in IgG's hinge region.~~	+	*<scene name='Rebecca_Martin/Sandbox1/Igg_disulfides/1'>IgG: disulfide bonds connecting the heavy and light chains</scene>

-	<scene name='Rebecca_Martin/Sandbox1/~~Igg_mutant~~/1'>IgG ~~with hinge deletion~~</scene> ~~(missing one fab fragment~~. ~~Note the T-shape. Compare with IgA2~~.	+	*<scene name='Rebecca_Martin/Sandbox1/Igg_glycines/1'>IgG: glycines (black)</scene> increase hinge flexibility. There are no proline residues in IgG's hinge region.

-	<scene name='Rebecca_Martin/Sandbox1/Igg_mutant_no_disulfie/1'>Lack of a disulfide bond between heavy and light chains in above IgG	+	*<scene name='Rebecca_Martin/Sandbox1/Igg_mutant/1'>IgG with hinge deletion</scene> (missing one fab fragment. Note the T-shape. Compare with IgA2.
		+
		+	*<scene name='Rebecca_Martin/Sandbox1/Igg_mutant_no_disulfie/1'>Lack of a disulfide bond between heavy and light chains in above IgG
	</scene>		</scene>

-	<scene name='Rebecca_Martin/Sandbox1/Igm_pentamer/1'>IgM pentamer</scene>

-	<scene name='Rebecca_Martin/Sandbox1/~~Igm~~/1'>IgM</scene>	+	*<scene name='Rebecca_Martin/Sandbox1/Igm_pentamer/1'>IgM pentamer</scene>

-	<scene name='Rebecca_Martin/Sandbox1/~~Igd~~/1'>~~IgD~~</scene> ~~Hinge region is 64 amino acids in length. Note similarity to IgA1.~~	+	*<scene name='Rebecca_Martin/Sandbox1/Igm/1'>IgM</scene>
-	\|}	+

		+	*<scene name='Rebecca_Martin/Sandbox1/Igd/1'>IgD</scene> Hinge region is 64 amino acids in length. Note similarity to IgA1.

Alexander Berchansky at 13:15, 20 March 2013

Alexander Berchansky — Wed, 20 Mar 2013 13:15:54 GMT

←Older revision		Revision as of 13:15, 20 March 2013
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		+	<StructureSection load='1iga' size='450' side='right' scene='' caption=''>
	== Introduction to IgA ==		== Introduction to IgA ==
	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 <ref name="seven">PMID:17428798</ref>. As a first line of defense in maintenance the integrity our mucosa, the immune system manufactures and secretes dimeric IgA to neutralize pathogenic organisms <ref name="five">PMID:15111057</ref> and exclude the entry of commensals at the mucosal border <ref name="nineseven">PMID:19079336</ref>. In the serum, IgA functions as a second line of defense against pathogens that may breech the epithelial boundary <ref name="five" />. The body produces more IgA than any other antibody isotype <ref name="nineseven"/>. In fact, IgA is the most abundant antibody in the body, further illustrating IgA's critical role in immunity <ref name="ten">PMID:10064707</ref>.		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 <ref name="seven">PMID:17428798</ref>. As a first line of defense in maintenance the integrity our mucosa, the immune system manufactures and secretes dimeric IgA to neutralize pathogenic organisms <ref name="five">PMID:15111057</ref> and exclude the entry of commensals at the mucosal border <ref name="nineseven">PMID:19079336</ref>. In the serum, IgA functions as a second line of defense against pathogens that may breech the epithelial boundary <ref name="five" />. The body produces more IgA than any other antibody isotype <ref name="nineseven"/>. In fact, IgA is the most abundant antibody in the body, further illustrating IgA's critical role in immunity <ref name="ten">PMID:10064707</ref>.
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	'''Overall Structure'''		'''Overall Structure'''
-	<applet load='1iga' size='400' frame='true' align='right' caption='Forms of IgA' />
	:An antibody is a tetramer of <scene name='Rebecca_Martin/Sandbox1/Iga1_light_chains/2'>2 light chains</scene> and <scene name='Rebecca_Martin/Sandbox1/Iga1_heavy_chains/1'>2 heavy chains</scene>. In other words, the antibody is a <scene name='Rebecca_Martin/Sandbox1/Iga1_no_spin/1'>homodimer</scene> of 2 heterodimers. Each <scene name='Rebecca_Martin/Sandbox1/Iga1_homodimer/1'>heterodimer</scene> is comprised on one light chain and one heavy chain. Heavy and light chains are held together with disulfide bonds and noncovalent interactions.		:An antibody is a tetramer of <scene name='Rebecca_Martin/Sandbox1/Iga1_light_chains/2'>2 light chains</scene> and <scene name='Rebecca_Martin/Sandbox1/Iga1_heavy_chains/1'>2 heavy chains</scene>. In other words, the antibody is a <scene name='Rebecca_Martin/Sandbox1/Iga1_no_spin/1'>homodimer</scene> of 2 heterodimers. Each <scene name='Rebecca_Martin/Sandbox1/Iga1_homodimer/1'>heterodimer</scene> is comprised on one light chain and one heavy chain. Heavy and light chains are held together with disulfide bonds and noncovalent interactions.

Jaime Prilusky at 06:41, 21 September 2010

Jaime Prilusky — Tue, 21 Sep 2010 06:41:07 GMT

←Older revision		Revision as of 06:41, 21 September 2010
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	:: TCR: Crystal Structure of the G17E/A52V/S54N/Q72H/E80V/L81S/T87S/G96V variant of the murine T cell receptor V beta 8.2 domain [[2apv]]		:: TCR: Crystal Structure of the G17E/A52V/S54N/Q72H/E80V/L81S/T87S/G96V variant of the murine T cell receptor V beta 8.2 domain [[2apv]]
	* V-type immunoglobulin examples		* V-type immunoglobulin examples
-	:: Crystal Structure of a Ligand-Binding Domain of the Human Polymeric Ig Receptor, pIgR [[~~1XED~~]]	+	:: Crystal Structure of a Ligand-Binding Domain of the Human Polymeric Ig Receptor, pIgR [[1xed]]
-	:: Crystal structure of human FcaRI [[~~10vz~~]]	+	:: Crystal structure of human FcaRI [[1ovz]]
-	:: Influenza virus hemagglutinin complexed with a neutralizing antibody [[~~1QFU~~]]	+	:: Influenza virus hemagglutinin complexed with a neutralizing antibody [[1qfu]]

	== References ==		== References ==