5whk - Revision history

OCA at 14:13, 4 October 2023

OCA — Wed, 04 Oct 2023 14:13:06 GMT

←Older revision		Revision as of 14:13, 4 October 2023
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	==Crystal structure of Fab fragment of antibody DX-2507 bound to FcRn-B2M==		==Crystal structure of Fab fragment of antibody DX-2507 bound to FcRn-B2M==
-	<StructureSection load='5whk' size='340' side='right' caption='[[5whk]], [[Resolution\|resolution]] 2.50Å' scene=''>	+	<StructureSection load='5whk' size='340' side='right'caption='[[5whk]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5whk]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WHK OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5WHK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5whk]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WHK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WHK FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=EDO:1,2~~-~~ETHANEDIOL'>EDO</scene>~~, ~~<scene name='pdbligand=NHE:2-~~[~~N-CYCLOHEXYLAMINO~~]~~ETHANE+SULFONIC+ACID'>NHE</scene>~~</td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.5Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~FCGRT, FCRN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode~~=~~Info&srchmode~~=~~5&id=9606 HUMAN])~~, ~~B2M~~, ~~CDABP0092, HDCMA22P ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode~~=~~Info&srchmode~~=~~5&id=9606 HUMAN~~])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5whk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5whk OCA], [~~http~~://pdbe.org/5whk PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5whk RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5whk PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5whk ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5whk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5whk OCA], [https://pdbe.org/5whk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5whk RCSB], [https://www.ebi.ac.uk/pdbsum/5whk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5whk ProSAT]</span></td></tr>
	</table>		</table>
-	== Disease ==
-	[[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[http://omim.org/entry/241600 241600]]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.<ref>PMID:16549777</ref> Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.<ref>PMID:3532124</ref> <ref>PMID:1336137</ref> <ref>PMID:7554280</ref> <ref>PMID:4586824</ref> <ref>PMID:8084451</ref> <ref>PMID:12119416</ref> <ref>PMID:12796775</ref> <ref>PMID:16901902</ref> <ref>PMID:16491088</ref> <ref>PMID:17646174</ref> <ref>PMID:18835253</ref> <ref>PMID:18395224</ref> <ref>PMID:19284997</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/~~B2MG_HUMAN B2MG_HUMAN~~]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. [[http://www.uniprot.org/uniprot/FCGRN_HUMAN FCGRN_HUMAN]] Binds to the Fc region of monomeric immunoglobulins gamma. Mediates the uptake of IgG from milk. Possible role in transfer of immunoglobulin G from mother to fetus.	+	[https://www.uniprot.org/uniprot/S6BAN1_HUMAN S6BAN1_HUMAN]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5whk" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5whk" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Beta-2 microglobulin 3D structures\|Beta-2 microglobulin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Clifton, M C~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Edwards, T E~~]]	+	[[Category: Clifton MC]]
-	[[Category: ~~Kenniston, J A~~]]	+	[[Category: Edwards TE]]
-	[[Category: ~~Nixon, A E~~]]	+	[[Category: Kenniston JA]]
-	[[Category: ~~Antibody recycling]]~~	+	[[Category: Nixon AE]]
-	~~[[Category: Fc]]~~	+
-	~~[[Category: Immune system]]~~	+
-	~~[[Category: Neonatal receptor~~]]	+

OCA at 07:56, 21 March 2018

OCA — Wed, 21 Mar 2018 07:56:33 GMT

←Older revision		Revision as of 07:56, 21 March 2018
Line 3:		Line 3:
	<StructureSection load='5whk' size='340' side='right' caption='[[5whk]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='5whk' size='340' side='right' caption='[[5whk]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5whk]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WHK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WHK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5whk]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WHK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WHK FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FCGRT, FCRN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), B2M, CDABP0092, HDCMA22P ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5whk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5whk OCA], [http://pdbe.org/5whk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5whk RCSB], [http://www.ebi.ac.uk/pdbsum/5whk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5whk ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5whk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5whk OCA], [http://pdbe.org/5whk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5whk RCSB], [http://www.ebi.ac.uk/pdbsum/5whk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5whk ProSAT]</span></td></tr>
	</table>		</table>
Line 11:		Line 12:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. [[http://www.uniprot.org/uniprot/FCGRN_HUMAN FCGRN_HUMAN]] Binds to the Fc region of monomeric immunoglobulins gamma. Mediates the uptake of IgG from milk. Possible role in transfer of immunoglobulin G from mother to fetus.		[[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. [[http://www.uniprot.org/uniprot/FCGRN_HUMAN FCGRN_HUMAN]] Binds to the Fc region of monomeric immunoglobulins gamma. Mediates the uptake of IgG from milk. Possible role in transfer of immunoglobulin G from mother to fetus.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The neonatal Fc receptor FcRn plays a critical role in the trafficking of IgGs across tissue barriers and in retaining high circulating concentrations of both IgG and albumin. Although generally beneficial from an immunological perspective in maintaining IgG populations, FcRn can contribute to the pathogenesis of autoimmune disorders when an abnormal immune response targets normal biological components. We previously described a monoclonal antibody (DX-2507) that binds to FcRn with high affinity at both neutral and acidic pH, prevents the simultaneous binding of IgG, and reduces circulating IgG levels in preclinical animal models. Here, we report a 2.5 A resolution X-ray crystal structure of an FcRn-DX-2507 Fab complex, revealing a nearly complete overlap of the IgG-Fc binding site in FcRn by complementarity-determining regions in DX-2507. This overlap explains how DX-2507 blocks IgG binding to FcRn and thereby shortens IgG half-life by preventing IgGs from recycling back into circulation. Moreover, the complex structure explains how the DX-2507 interaction is pH-insensitive unlike normal Fc interactions and how serum albumin levels are unaffected by DX-2507 binding. These structural studies could inform antibody-based therapeutic approaches for limiting the effects of IgG-mediated autoimmune disease.
		+
		+	Structural basis for pH-insensitive inhibition of immunoglobulin G recycling by an anti-neonatal Fc receptor antibody.,Kenniston JA, Taylor BM, Conley GP, Cosic J, Kopacz KJ, Lindberg AP, Comeau SR, Atkins K, Bullen J, TenHoor C, Adelman BA, Sexton DJ, Edwards TE, Nixon AE J Biol Chem. 2017 Oct 20;292(42):17449-17460. doi: 10.1074/jbc.M117.807396. Epub , 2017 Sep 6. PMID:28878017<ref>PMID:28878017</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5whk" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Clifton, M C]]		[[Category: Clifton, M C]]
	[[Category: Edwards, T E]]		[[Category: Edwards, T E]]

OCA: Protected "5whk" [edit=sysop:move=sysop]

OCA — Wed, 13 Sep 2017 09:39:44 GMT

Protected "5whk" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:39, 13 September 2017

OCA: New page: ==Crystal structure of Fab fragment of antibody DX-2507 bound to FcRn-B2M==
OCA — Wed, 13 Sep 2017 09:39:41 GMT

New page: ==Crystal structure of Fab fragment of antibody DX-2507 bound to FcRn-B2M== <StructureSection load='5whk' size='340' side='right' caption='5whk, resolution 2.50Å'...

New page

==Crystal structure of Fab fragment of antibody DX-2507 bound to FcRn-B2M==
<StructureSection load='5whk' size='340' side='right' caption='[[5whk]], [[Resolution|resolution]] 2.50Å' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5whk]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WHK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WHK FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5whk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5whk OCA], [http://pdbe.org/5whk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5whk RCSB], [http://www.ebi.ac.uk/pdbsum/5whk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5whk ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[http://omim.org/entry/241600 241600]]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.<ref>PMID:16549777</ref> Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.<ref>PMID:3532124</ref> <ref>PMID:1336137</ref> <ref>PMID:7554280</ref> <ref>PMID:4586824</ref> <ref>PMID:8084451</ref> <ref>PMID:12119416</ref> <ref>PMID:12796775</ref> <ref>PMID:16901902</ref> <ref>PMID:16491088</ref> <ref>PMID:17646174</ref> <ref>PMID:18835253</ref> <ref>PMID:18395224</ref> <ref>PMID:19284997</ref>
== Function ==
[[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. [[http://www.uniprot.org/uniprot/FCGRN_HUMAN FCGRN_HUMAN]] Binds to the Fc region of monomeric immunoglobulins gamma. Mediates the uptake of IgG from milk. Possible role in transfer of immunoglobulin G from mother to fetus.
== References ==
<references/>
TOC
</StructureSection>
[[Category: Clifton, M C]]
[[Category: Edwards, T E]]
[[Category: Kenniston, J A]]
[[Category: Nixon, A E]]
[[Category: Antibody recycling]]
[[Category: Fc]]
[[Category: Immune system]]
[[Category: Neonatal receptor]]