6qly - Revision history

OCA at 12:03, 24 January 2024

OCA — Wed, 24 Jan 2024 12:03:29 GMT

←Older revision		Revision as of 12:03, 24 January 2024
Line 3:		Line 3:
	<StructureSection load='6qly' size='340' side='right'caption='[[6qly]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='6qly' size='340' side='right'caption='[[6qly]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qly]] is a 1 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=6QLY OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6QLY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qly]] is a 1 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=6QLY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QLY FirstGlance]. <br>
-	</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=SO4:SULFATE+ION'>SO4</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"~~>MYLIP, BZF1, IDOL, BM-023, PP5242 ([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=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks~~'>~~[http://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27]~~ </~~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=6qly FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qly OCA], [https://pdbe.org/6qly PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qly RCSB], [https://www.ebi.ac.uk/pdbsum/6qly PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qly 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=6qly FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qly OCA], [~~http~~://pdbe.org/6qly PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6qly RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6qly PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6qly ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/MYLIP_HUMAN MYLIP_HUMAN]] E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8. Activity depends on E2 enzymes of the UBE2D family. Proteasomal degradation of MRLC leads to inhibit neurite outgrowth in presence of NGF by counteracting the stabilization of MRLC by saposin-like protein (CNPY2/MSAP) and reducing CNPY2-stimulated neurite outgrowth. Acts as a sterol-dependent inhibitor of cellular cholesterol uptake by mediating ubiquitination and subsequent degradation of LDLR.<ref>PMID:10593918</ref> <ref>PMID:14550572</ref> <ref>PMID:12826659</ref> <ref>PMID:19520913</ref> <ref>PMID:20427281</ref> <ref>PMID:22109552</ref>	+	[https://www.uniprot.org/uniprot/MYLIP_HUMAN MYLIP_HUMAN] E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8. Activity depends on E2 enzymes of the UBE2D family. Proteasomal degradation of MRLC leads to inhibit neurite outgrowth in presence of NGF by counteracting the stabilization of MRLC by saposin-like protein (CNPY2/MSAP) and reducing CNPY2-stimulated neurite outgrowth. Acts as a sterol-dependent inhibitor of cellular cholesterol uptake by mediating ubiquitination and subsequent degradation of LDLR.<ref>PMID:10593918</ref> <ref>PMID:14550572</ref> <ref>PMID:12826659</ref> <ref>PMID:19520913</ref> <ref>PMID:20427281</ref> <ref>PMID:22109552</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: RING-type E3 ubiquitin transferase]]~~	+	[[Category: Martinelli L]]
-	[[Category: Martinelli, L]]	+	[[Category: Sixma TK]]
-	[[Category: Sixma~~, T K]]~~	+
-	~~[[Category: Ferm domain]]~~	+
-	~~[[Category: Ldlr degradation]]~~	+
-	~~[[Category: Ligase]]~~	+
-	~~[[Category: Ubiquitin e3 ligase cholesterol metabolism~~]]	+

OCA at 09:58, 12 August 2020

OCA — Wed, 12 Aug 2020 09:58:14 GMT

←Older revision		Revision as of 09:58, 12 August 2020
Line 3:		Line 3:
	<StructureSection load='6qly' size='340' side='right'caption='[[6qly]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='6qly' size='340' side='right'caption='[[6qly]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qly]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QLY OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6QLY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qly]] is a 1 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=6QLY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6QLY 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=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</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=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MYLIP, BZF1, IDOL, BM-023, PP5242 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </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=6qly FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qly OCA], [http://pdbe.org/6qly PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qly RCSB], [http://www.ebi.ac.uk/pdbsum/6qly PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qly 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=6qly FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qly OCA], [http://pdbe.org/6qly PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qly RCSB], [http://www.ebi.ac.uk/pdbsum/6qly PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qly ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/MYLIP_HUMAN MYLIP_HUMAN]] E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8. Activity depends on E2 enzymes of the UBE2D family. Proteasomal degradation of MRLC leads to inhibit neurite outgrowth in presence of NGF by counteracting the stabilization of MRLC by saposin-like protein (CNPY2/MSAP) and reducing CNPY2-stimulated neurite outgrowth. Acts as a sterol-dependent inhibitor of cellular cholesterol uptake by mediating ubiquitination and subsequent degradation of LDLR.<ref>PMID:10593918</ref> <ref>PMID:14550572</ref> <ref>PMID:12826659</ref> <ref>PMID:19520913</ref> <ref>PMID:20427281</ref> <ref>PMID:22109552</ref>		[[http://www.uniprot.org/uniprot/MYLIP_HUMAN MYLIP_HUMAN]] E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8. Activity depends on E2 enzymes of the UBE2D family. Proteasomal degradation of MRLC leads to inhibit neurite outgrowth in presence of NGF by counteracting the stabilization of MRLC by saposin-like protein (CNPY2/MSAP) and reducing CNPY2-stimulated neurite outgrowth. Acts as a sterol-dependent inhibitor of cellular cholesterol uptake by mediating ubiquitination and subsequent degradation of LDLR.<ref>PMID:10593918</ref> <ref>PMID:14550572</ref> <ref>PMID:12826659</ref> <ref>PMID:19520913</ref> <ref>PMID:20427281</ref> <ref>PMID:22109552</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Hepatic abundance of the Low-Density lipoprotein receptor (LDLR) is a critical determinant of circulating plasma LDL-cholesterol levels and hence development of coronary artery disease. The sterol-responsive E3 ubiquitin ligase Inducible Degrader of the LDLR (IDOL) specifically promotes ubiquitination and subsequent lysosomal degradation of the LDLR and thus controls cellular LDL uptake. IDOL contains an extended N-terminal FERM (F for 4.1 protein, E for ezrin, R for radixin and M for moesin) domain, responsible for substrate recognition and plasma-membrane association, and a second C-terminal RING domain, responsible for the E3 ligase activity and homo-dimerization. As IDOL is a putative lipid-lowering drug-target we investigated the molecular details of its substrate recognition. We produced and isolated full-length IDOL protein, which displayed high auto-ubiquitination activity. However, in vitro ubiquitination of its substrate, the intracellular tail of the LDLR, was low. To investigate the structural basis for this we determined crystal structures of the extended FERM domain of IDOL and multiple conformations of its F3ab subdomain. These reveal the archetypal F1-F2-F3 tri-lobed FERM domain structure but show that the F3c subdomain orientation obscures the target binding site. To substantiate this finding, we analyzed the full length FERM domain and a series of truncated FERM constructs by small angle X-ray scattering (SAXS). The scattering data support a compact and globular core FERM domain with a more flexible and extended C-terminal region. This flexibility may explain the low activity in vitro and suggests that IDOL may require activation for recognition of the LDLR.
		+
		+	Structural analysis of the LDL receptor-interacting FERM domain in the E3 ubiquitin ligase IDOL reveals an obscured substrate binding site.,Martinelli L, Adamopoulos A, Johansson P, Wan PT, Gunnarsson J, Guo H, Boyd H, Zelcer N, Sixma TK J Biol Chem. 2020 Jul 29. pii: RA120.014349. doi: 10.1074/jbc.RA120.014349. PMID:32727844<ref>PMID:32727844</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6qly" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Ubiquitin protein ligase 3D structures\|Ubiquitin protein ligase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: RING-type E3 ubiquitin transferase]]		[[Category: RING-type E3 ubiquitin transferase]]

OCA at 06:29, 19 February 2020

OCA — Wed, 19 Feb 2020 06:29:04 GMT

←Older revision		Revision as of 06:29, 19 February 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6qly is ~~ON HOLD~~	+	==IDOL FERM domain==
-		+	<StructureSection load='6qly' size='340' side='right'caption='[[6qly]], [[Resolution\|resolution]] 2.50Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6qly]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QLY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QLY FirstGlance]. <br>
-	~~Description~~:	+	</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=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </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=6qly FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qly OCA], [http://pdbe.org/6qly PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qly RCSB], [http://www.ebi.ac.uk/pdbsum/6qly PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qly ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MYLIP_HUMAN MYLIP_HUMAN]] E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8. Activity depends on E2 enzymes of the UBE2D family. Proteasomal degradation of MRLC leads to inhibit neurite outgrowth in presence of NGF by counteracting the stabilization of MRLC by saposin-like protein (CNPY2/MSAP) and reducing CNPY2-stimulated neurite outgrowth. Acts as a sterol-dependent inhibitor of cellular cholesterol uptake by mediating ubiquitination and subsequent degradation of LDLR.<ref>PMID:10593918</ref> <ref>PMID:14550572</ref> <ref>PMID:12826659</ref> <ref>PMID:19520913</ref> <ref>PMID:20427281</ref> <ref>PMID:22109552</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: RING-type E3 ubiquitin transferase]]
		+	[[Category: Martinelli, L]]
		+	[[Category: Sixma, T K]]
		+	[[Category: Ferm domain]]
		+	[[Category: Ldlr degradation]]
		+	[[Category: Ligase]]
		+	[[Category: Ubiquitin e3 ligase cholesterol metabolism]]

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

OCA — Wed, 13 Feb 2019 08:04:51 GMT

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

←Older revision

Revision as of 08:04, 13 February 2019

OCA: New page: '''Unreleased structure''' The entry 6qly is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 13 Feb 2019 08:04:49 GMT

New page: '''Unreleased structure''' The entry 6qly is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6qly is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]