6avu - Revision history

OCA at 14:18, 13 March 2024

OCA — Wed, 13 Mar 2024 14:18:42 GMT

←Older revision		Revision as of 14:18, 13 March 2024
Line 3:		Line 3:
	<SX load='6avu' size='340' side='right' viewer='molstar' caption='[[6avu]], [[Resolution\|resolution]] 35.00Å' scene=''>		<SX load='6avu' size='340' side='right' viewer='molstar' caption='[[6avu]], [[Resolution\|resolution]] 35.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6avu]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~] and [~~http~~://en.wikipedia.org/wiki/~~Lk3_transgenic_mice Lk3 transgenic mice~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AVU OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6AVU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6avu]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AVU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AVU FirstGlance]. <br>
-	</td></tr><tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~>[[5opy\|5opy]], [[6avq\|6avq]], [[6avr\|6avr]]</td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 35Å</td></tr>
-	~~<tr~~ id~~='gene'><td class~~="~~sblockLbl~~">~~<b>~~[[~~Gene~~\|~~Gene:~~]]~~</b></td><td class="sblockDat">ITGAV, MSK8, VNRA, VTNR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info~~&~~srchmode=5&id=9606 HUMAN]), ITGB3, GP3A ([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'>[https://proteopedia.org/fgij/fg.htm?mol=6avu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6avu OCA], [https://pdbe.org/6avu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6avu RCSB], [https://www.ebi.ac.uk/pdbsum/6avu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6avu ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6avu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6avu OCA], [~~http~~://pdbe.org/6avu PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6avu RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6avu PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6avu ProSAT]</span></td></tr>	+
	</table>		</table>
-	== Disease ==
-	[[http://www.uniprot.org/uniprot/ITB3_HUMAN ITB3_HUMAN]] Defects in ITGB3 are a cause of Glanzmann thrombasthenia (GT) [MIM:[http://omim.org/entry/273800 273800]]; also known as thrombasthenia of Glanzmann and Naegeli. GT is the most common inherited disease of platelets. It is an autosomal recessive disorder characterized by mucocutaneous bleeding of mild-to-moderate severity and the inability of this integrin to recognize macromolecular or synthetic peptide ligands. GT has been classified clinically into types I and II. In type I, platelets show absence of the glycoprotein IIb/beta-3 complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express the glycoprotein IIb/beta-3 complex at reduced levels (5-20% controls), have detectable amounts of fibrinogen, and have low or moderate clot retraction capability. The platelets of GT 'variants' have normal or near normal (60-100%) expression of dysfunctional receptors.<ref>PMID:2392682</ref> <ref>PMID:1371279</ref> <ref>PMID:1602006</ref> <ref>PMID:1438206</ref> <ref>PMID:8781422</ref> <ref>PMID:9376589</ref> <ref>PMID:9215749</ref> <ref>PMID:9790984</ref> <ref>PMID:9684783</ref> <ref>PMID:10233432</ref> <ref>PMID:11588040</ref> <ref>PMID:11897046</ref> <ref>PMID:12083483</ref> <ref>PMID:12353082</ref> <ref>PMID:15583747</ref> <ref>PMID:15634267</ref> <ref>PMID:15748237</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/ITAV_HUMAN ITAV_HUMAN]] The alpha-V integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin and vWF. They recognize the sequence R-G-D in a wide array of ligands. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions. [[http://www.uniprot.org/uniprot/ITB3_HUMAN ITB3_HUMAN]] Integrin alpha-V/beta-3 is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIb/beta-3 and alpha-V/beta-3 recognize the sequence R-G-D in a wide array of ligands. Integrin alpha-IIb/beta-3 recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial surface. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.	+	[https://www.uniprot.org/uniprot/ITAV_HUMAN ITAV_HUMAN] The alpha-V integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin and vWF. They recognize the sequence R-G-D in a wide array of ligands. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	The LM609 antibody specifically recognizes alphaVbeta3 integrin and inhibits angiogenesis, bone resorption, and viral infections in an arginine-glycine-aspartate-independent manner. LM609 entered phase II clinical trials for the treatment of several cancers and was also used for alphaVbeta3-targeted radioimmunotherapy. To elucidate the mechanisms of recognition and inhibition of alphaVbeta3 integrin, we solved the structure of the LM609 antigen-binding fragment by X-ray crystallography and determined its binding affinity for alphaVbeta3. Using single-particle electron microscopy, we show that LM609 binds at the interface between the beta-propeller domain of the alphaV chain and the betaI domain of the beta3 chain, near the RGD-binding site, of all observed integrin conformational states. Integrating these data with fluorescence size-exclusion chromatography, we demonstrate that LM609 sterically hinders access of large ligands to the RGD-binding pocket, without obstructing it. This work provides a structural framework to expedite future efforts utilizing LM609 as a diagnostic or therapeutic tool.	+
-		+
-	The Therapeutic Antibody LM609 Selectively Inhibits Ligand Binding to Human alphaVbeta3 Integrin via Steric Hindrance.,Borst AJ, James ZM, Zagotta WN, Ginsberg M, Rey FA, DiMaio F, Backovic M, Veesler D Structure. 2017 Oct 7. pii: S0969-2126(17)30298-8. doi:, 10.1016/j.str.2017.09.007. PMID:29033288<ref>PMID:29033288</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 6avu" style="background-color:#fffaf0;"></div>~~	+

	==See Also==		==See Also==
		+	*[[Antibody 3D structures\|Antibody 3D structures]]
	*[[Integrin 3D structures\|Integrin 3D structures]]		*[[Integrin 3D structures\|Integrin 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</SX>		</SX>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Lk3 transgenic mice~~]]	+	[[Category: Mus musculus]]
-	[[Category: Backovic, M]]	+	[[Category: Backovic M]]
-	[[Category: Borst~~, A J~~]]	+	[[Category: Borst AJ]]
-	[[Category: DiMaio, F]]	+	[[Category: DiMaio F]]
-	[[Category: Ginsberg, M]]	+	[[Category: Ginsberg M]]
-	[[Category: James~~, Z N~~]]	+	[[Category: James ZN]]
-	[[Category: Rey~~, F A~~]]	+	[[Category: Rey FA]]
-	[[Category: Veesler, D]]	+	[[Category: Veesler D]]
-	[[Category: Zagotta~~, W N]]~~	+	[[Category: Zagotta WN]]
-	~~[[Category: Abegrin]]~~	+
-	~~[[Category: Alpha-v beta-3 integrin]]~~	+
-	~~[[Category: Lm609]]~~	+
-	~~[[Category: Signaling protein]]~~	+
-	~~[[Category: Vitaxin~~]]	+

OCA at 23:10, 10 April 2020

OCA — Fri, 10 Apr 2020 23:10:31 GMT

←Older revision		Revision as of 23:10, 10 April 2020
Line 3:		Line 3:
	<SX load='6avu' size='340' side='right' viewer='molstar' caption='[[6avu]], [[Resolution\|resolution]] 35.00Å' scene=''>		<SX load='6avu' size='340' side='right' viewer='molstar' caption='[[6avu]], [[Resolution\|resolution]] 35.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6avu]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AVU OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6AVU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6avu]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AVU OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6AVU FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5opy\|5opy]], [[6avq\|6avq]], [[6avr\|6avr]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5opy\|5opy]], [[6avq\|6avq]], [[6avr\|6avr]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ITGAV, MSK8, VNRA, VTNR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ITGB3, GP3A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ITGAV, MSK8, VNRA, VTNR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ITGB3, GP3A ([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=6avu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6avu OCA], [http://pdbe.org/6avu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6avu RCSB], [http://www.ebi.ac.uk/pdbsum/6avu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6avu ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6avu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6avu OCA], [http://pdbe.org/6avu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6avu RCSB], [http://www.ebi.ac.uk/pdbsum/6avu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6avu ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==

OCA at 20:26, 6 March 2020

OCA — Fri, 06 Mar 2020 20:26:06 GMT

←Older revision		Revision as of 20:26, 6 March 2020
Line 1:		Line 1:

	==Human alpha-V beta-3 Integrin (open conformation) in complex with the therapeutic antibody LM609==		==Human alpha-V beta-3 Integrin (open conformation) in complex with the therapeutic antibody LM609==
-	<~~StructureSection~~ load='6avu' size='340' side='right' caption='[[6avu]], [[Resolution\|resolution]] 35.00Å' scene=''>	+	<SX load='6avu' size='340' side='right' viewer='molstar' caption='[[6avu]], [[Resolution\|resolution]] 35.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6avu]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AVU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AVU FirstGlance]. <br>		<table><tr><td colspan='2'>[[6avu]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AVU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AVU FirstGlance]. <br>
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 6avu" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6avu" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Integrin 3D structures\|Integrin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
-	</~~StructureSection~~>	+	</SX>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Lk3 transgenic mice]]		[[Category: Lk3 transgenic mice]]
	[[Category: Backovic, M]]		[[Category: Backovic, M]]

OCA at 10:18, 15 November 2017

OCA — Wed, 15 Nov 2017 10:18:37 GMT

←Older revision		Revision as of 10:18, 15 November 2017
Line 3:		Line 3:
	<StructureSection load='6avu' size='340' side='right' caption='[[6avu]], [[Resolution\|resolution]] 35.00Å' scene=''>		<StructureSection load='6avu' size='340' side='right' caption='[[6avu]], [[Resolution\|resolution]] 35.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6avu]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AVU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AVU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6avu]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AVU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AVU FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5opy\|5opy]], [[6avq\|6avq]], [[6avr\|6avr]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5opy\|5opy]], [[6avq\|6avq]], [[6avr\|6avr]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ITGAV, MSK8, VNRA, VTNR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ITGB3, GP3A ([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=6avu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6avu OCA], [http://pdbe.org/6avu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6avu RCSB], [http://www.ebi.ac.uk/pdbsum/6avu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6avu 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=6avu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6avu OCA], [http://pdbe.org/6avu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6avu RCSB], [http://www.ebi.ac.uk/pdbsum/6avu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6avu ProSAT]</span></td></tr>
	</table>		</table>
Line 24:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Lk3 transgenic mice]]
	[[Category: Backovic, M]]		[[Category: Backovic, M]]
	[[Category: Borst, A J]]		[[Category: Borst, A J]]

OCA at 06:15, 1 November 2017

OCA — Wed, 01 Nov 2017 06:15:42 GMT

←Older revision		Revision as of 06:15, 1 November 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6avu is ~~ON HOLD~~	+	==Human alpha-V beta-3 Integrin (open conformation) in complex with the therapeutic antibody LM609==
		+	<StructureSection load='6avu' size='340' side='right' caption='[[6avu]], [[Resolution\|resolution]] 35.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6avu]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AVU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AVU FirstGlance]. <br>
		+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5opy\|5opy]], [[6avq\|6avq]], [[6avr\|6avr]]</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=6avu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6avu OCA], [http://pdbe.org/6avu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6avu RCSB], [http://www.ebi.ac.uk/pdbsum/6avu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6avu ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/ITB3_HUMAN ITB3_HUMAN]] Defects in ITGB3 are a cause of Glanzmann thrombasthenia (GT) [MIM:[http://omim.org/entry/273800 273800]]; also known as thrombasthenia of Glanzmann and Naegeli. GT is the most common inherited disease of platelets. It is an autosomal recessive disorder characterized by mucocutaneous bleeding of mild-to-moderate severity and the inability of this integrin to recognize macromolecular or synthetic peptide ligands. GT has been classified clinically into types I and II. In type I, platelets show absence of the glycoprotein IIb/beta-3 complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express the glycoprotein IIb/beta-3 complex at reduced levels (5-20% controls), have detectable amounts of fibrinogen, and have low or moderate clot retraction capability. The platelets of GT 'variants' have normal or near normal (60-100%) expression of dysfunctional receptors.<ref>PMID:2392682</ref> <ref>PMID:1371279</ref> <ref>PMID:1602006</ref> <ref>PMID:1438206</ref> <ref>PMID:8781422</ref> <ref>PMID:9376589</ref> <ref>PMID:9215749</ref> <ref>PMID:9790984</ref> <ref>PMID:9684783</ref> <ref>PMID:10233432</ref> <ref>PMID:11588040</ref> <ref>PMID:11897046</ref> <ref>PMID:12083483</ref> <ref>PMID:12353082</ref> <ref>PMID:15583747</ref> <ref>PMID:15634267</ref> <ref>PMID:15748237</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ITAV_HUMAN ITAV_HUMAN]] The alpha-V integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin and vWF. They recognize the sequence R-G-D in a wide array of ligands. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions. [[http://www.uniprot.org/uniprot/ITB3_HUMAN ITB3_HUMAN]] Integrin alpha-V/beta-3 is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIb/beta-3 and alpha-V/beta-3 recognize the sequence R-G-D in a wide array of ligands. Integrin alpha-IIb/beta-3 recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial surface. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The LM609 antibody specifically recognizes alphaVbeta3 integrin and inhibits angiogenesis, bone resorption, and viral infections in an arginine-glycine-aspartate-independent manner. LM609 entered phase II clinical trials for the treatment of several cancers and was also used for alphaVbeta3-targeted radioimmunotherapy. To elucidate the mechanisms of recognition and inhibition of alphaVbeta3 integrin, we solved the structure of the LM609 antigen-binding fragment by X-ray crystallography and determined its binding affinity for alphaVbeta3. Using single-particle electron microscopy, we show that LM609 binds at the interface between the beta-propeller domain of the alphaV chain and the betaI domain of the beta3 chain, near the RGD-binding site, of all observed integrin conformational states. Integrating these data with fluorescence size-exclusion chromatography, we demonstrate that LM609 sterically hinders access of large ligands to the RGD-binding pocket, without obstructing it. This work provides a structural framework to expedite future efforts utilizing LM609 as a diagnostic or therapeutic tool.

-	~~Authors:~~ Borst~~, A.J.~~, James~~, Z.N.~~, Zagotta~~, W.N.~~, Ginsberg, M., Rey~~, F.A.~~, DiMaio, F., Backovic, M., Veesler, D.	+	The Therapeutic Antibody LM609 Selectively Inhibits Ligand Binding to Human alphaVbeta3 Integrin via Steric Hindrance.,Borst AJ, James ZM, Zagotta WN, Ginsberg M, Rey FA, DiMaio F, Backovic M, Veesler D Structure. 2017 Oct 7. pii: S0969-2126(17)30298-8. doi:, 10.1016/j.str.2017.09.007. PMID:29033288<ref>PMID:29033288</ref>

-	~~Description: Human alpha-V beta-3 Integrin (open conformation) in complex with~~ the ~~therapeutic antibody LM609~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
		+	<div class="pdbe-citations 6avu" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Backovic, M]]		[[Category: Backovic, M]]
-	[[Category: ~~Veesler~~, D]]	+	[[Category: Borst, A J]]
-	[[Category: ~~Zagotta~~, ~~W.N]]~~	+	[[Category: DiMaio, F]]
-	~~[[Category: James, Z.N~~]]	+
	[[Category: Ginsberg, M]]		[[Category: Ginsberg, M]]
-	[[Category: ~~Borst~~, ~~A.J~~]]	+	[[Category: James, Z N]]
-	[[Category: Rey, F.A]]	+	[[Category: Rey, F A]]
-	[[Category: ~~Dimaio~~, F]]	+	[[Category: Veesler, D]]
		+	[[Category: Zagotta, W N]]
		+	[[Category: Abegrin]]
		+	[[Category: Alpha-v beta-3 integrin]]
		+	[[Category: Lm609]]
		+	[[Category: Signaling protein]]
		+	[[Category: Vitaxin]]

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

OCA — Wed, 27 Sep 2017 16:51:04 GMT

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

←Older revision

Revision as of 16:51, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 6avu is ON HOLD Authors: Borst, A.J., James, Z.N., Zagotta, W.N., Ginsberg, M., Rey, F.A., DiMaio, F., Backovic, M., Veesler, D. Description: Human...

OCA — Wed, 27 Sep 2017 16:51:03 GMT

New page: '''Unreleased structure''' The entry 6avu is ON HOLD Authors: Borst, A.J., James, Z.N., Zagotta, W.N., Ginsberg, M., Rey, F.A., DiMaio, F., Backovic, M., Veesler, D. Description: Human...

New page

'''Unreleased structure'''

The entry 6avu is ON HOLD

Authors: Borst, A.J., James, Z.N., Zagotta, W.N., Ginsberg, M., Rey, F.A., DiMaio, F., Backovic, M., Veesler, D.

Description: Human alpha-V beta-3 Integrin (open conformation) in complex with the therapeutic antibody LM609
[[Category: Unreleased Structures]]
[[Category: Backovic, M]]
[[Category: Veesler, D]]
[[Category: Zagotta, W.N]]
[[Category: James, Z.N]]
[[Category: Ginsberg, M]]
[[Category: Borst, A.J]]
[[Category: Rey, F.A]]
[[Category: Dimaio, F]]