OCA at 12:12, 24 January 2024

2024-01-24T12:12:47Z

←Older revision		Revision as of 12:12, 24 January 2024
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-	'''Unreleased structure'''

-	The ~~entry~~ 6r0x is ~~ON HOLD~~	+	==The extracellular domain of G6b-B in complex with Fab fragment and DP12 heparin oligosaccharide.==
		+	<StructureSection load='6r0x' size='340' side='right'caption='[[6r0x]], [[Resolution\|resolution]] 3.13Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6r0x]] is a 6 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=6R0X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6R0X FirstGlance]. <br>
		+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 3.13Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A2G:N-ACETYL-2-DEOXY-2-AMINO-GALACTOSE'>A2G</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=IDS:2-O-SULFO-ALPHA-L-IDOPYRANURONIC+ACID'>IDS</scene>, <scene name='pdbligand=SGN:N,O6-DISULFO-GLUCOSAMINE'>SGN</scene>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene></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=6r0x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r0x OCA], [https://pdbe.org/6r0x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6r0x RCSB], [https://www.ebi.ac.uk/pdbsum/6r0x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6r0x ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/G6B_HUMAN G6B_HUMAN] The disease is caused by variants affecting the gene represented in this entry.
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/G6B_HUMAN G6B_HUMAN] Inhibitory receptor that acts as a critical regulator of hematopoietic lineage differentiation, megakaryocyte function and platelet production (PubMed:12665801, PubMed:17311996, PubMed:27743390). Inhibits platelet aggregation and activation by agonists such as ADP and collagen-related peptide (PubMed:12665801). This regulation of megakaryocate function as well as platelet production ann activation is done through the inhibition (via the 2 ITIM motifs) of the receptors CLEC1B and GP6:FcRgamma signaling (PubMed:17311996). Appears to operate in a calcium-independent manner (PubMed:12665801).<ref>PMID:12665801</ref> <ref>PMID:17311996</ref> <ref>PMID:27743390</ref> Isoform B, displayed in this entry, is the only isoform to contain both a transmembrane region and 2 immunoreceptor tyrosine-based inhibitor motifs (ITIMs) and, thus, the only one which probably has a role of inhibitory receptor. Isoform A may be the activating counterpart of isoform B.<ref>PMID:11544253</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The immunoreceptor tyrosine-based inhibition motif (ITIM)-containing receptor G6b-B is critical for platelet production and activation. Loss of G6b-B results in severe macrothrombocytopenia, myelofibrosis and aberrant platelet function in mice and humans. Using a combination of immunohistochemistry, affinity chromatography and proteomics, we identified the extracellular matrix heparan sulfate (HS) proteoglycan perlecan as a G6b-B binding partner. Subsequent in vitro biochemical studies and a cell-based genetic screen demonstrated that the interaction is specifically mediated by the HS chains of perlecan. Biophysical analysis revealed that heparin forms a high-affinity complex with G6b-B and mediates dimerization. Using platelets from humans and genetically modified mice, we demonstrate that binding of G6b-B to HS and multivalent heparin inhibits platelet and megakaryocyte function by inducing downstream signaling via the tyrosine phosphatases Shp1 and Shp2. Our findings provide novel insights into how G6b-B is regulated and contribute to our understanding of the interaction of megakaryocytes and platelets with glycans.

-	~~Authors: Ogg~~, D.J., McMiken, H.J., ~~Howard~~, T.D.	+	Heparan sulfates are critical regulators of the inhibitory megakaryocyte-platelet receptor G6b-B.,Vogtle T, Sharma S, Mori J, Nagy Z, Semeniak D, Scandola C, Geer MJ, Smith CW, Lane J, Pollack S, Lassila R, Jouppila A, Barr AJ, Ogg DJ, Howard TD, McMiken HJ, Warwicker J, Geh C, Rowlinson R, Abbott WM, Eckly A, Schulze H, Wright GJ, Mazharian A, Futterer K, Rajesh S, Douglas MR, Senis YA Elife. 2019 Aug 22;8:e46840. doi: 10.7554/eLife.46840. PMID:31436532<ref>PMID:31436532</ref>

-	~~Description: The extracellular domain~~ of ~~G6b-B in complex with Fab fragment and DP12 heparin oligosaccharide~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Mcmiken, H.J~~]]	+	<div class="pdbe-citations 6r0x" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Ogg, D.J~~]]	+
-	[[Category: ~~Howard, T.D~~]]	+	==See Also==
		+	*[[Antibody 3D structures\|Antibody 3D structures]]
		+	*[[3D structures of human antibody\|3D structures of human antibody]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Howard TD]]
		+	[[Category: McMiken HJ]]
		+	[[Category: Ogg DJ]]

OCA: Protected "6r0x" [edit=sysop:move=sysop]

2019-03-20T06:17:06Z

Protected "6r0x" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:17, 20 March 2019

OCA: New page: '''Unreleased structure''' The entry 6r0x is ON HOLD Authors: Ogg, D.J., McMiken, H.J., Howard, T.D. Description: The extracellular domain of G6b-B in complex with Fab fragment and DP1...

2019-03-20T06:17:05Z

New page: '''Unreleased structure''' The entry 6r0x is ON HOLD Authors: Ogg, D.J., McMiken, H.J., Howard, T.D. Description: The extracellular domain of G6b-B in complex with Fab fragment and DP1...

New page

'''Unreleased structure'''

The entry 6r0x is ON HOLD

Authors: Ogg, D.J., McMiken, H.J., Howard, T.D.

Description: The extracellular domain of G6b-B in complex with Fab fragment and DP12 heparin oligosaccharide.
[[Category: Unreleased Structures]]
[[Category: Mcmiken, H.J]]
[[Category: Ogg, D.J]]
[[Category: Howard, T.D]]

6r0x - Revision history

OCA at 12:12, 24 January 2024

OCA: Protected "6r0x" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6r0x is ON HOLD Authors: Ogg, D.J., McMiken, H.J., Howard, T.D. Description: The extracellular domain of G6b-B in complex with Fab fragment and DP1...