OCA at 10:07, 17 January 2024

OCA — Wed, 17 Jan 2024 10:07:44 GMT

←Older revision		Revision as of 10:07, 17 January 2024
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8pd0 is ~~ON HOLD until Paper~~ Publication	+	==cryo-EM structure of Doa10 in MSP1E3D1==
		+	<StructureSection load='8pd0' size='340' side='right'caption='[[8pd0]], [[Resolution\|resolution]] 3.58Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8pd0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8PD0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8PD0 FirstGlance]. <br>
		+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 3.58Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PCW:1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PCW</scene>, <scene name='pdbligand=PX6:1,2-DIPALMITOYL-SN-GLYCERO-3-PHOSPHATE'>PX6</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=8pd0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8pd0 OCA], [https://pdbe.org/8pd0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8pd0 RCSB], [https://www.ebi.ac.uk/pdbsum/8pd0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8pd0 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/DOA10_YEAST DOA10_YEAST] E3 ubiquitin-protein ligase which accepts ubiquitin specifically from endoplasmic reticulum-associated UBC6 and UBC7 E2 ligases, and transfers it to substrates promoting their degradation. Mediates the degradation of a broad range of substrates, inluding endoplasmic reticulum membrane proteins (ERQC), soluble nuclear proteins and soluble cytoplasmic proteins (CytoQC). Component of the DOA10 ubiquitin ligase complex, which is part of the ERAD-C pathway responsible for the rapid degradation of membrane proteins with misfolded cytoplasmic domains. ERAD-C substrates are ubiquitinated through DOA10 in conjunction with the E2 ubiquitin-conjugating enzymes UBC6 and UBC7-CUE1. Ubiquitinated substrates are then removed to the cytosol via the action of the UFD1-NPL4-CDC48/p97 (UNC) AAA ATPase complex and targeted to the proteasome. Also recognizes the N-terminally acetylated residue of proteins as degradation signal (degron). N-terminally acetylated target proteins include MATALPHA2, TBF1, SLK19, YMR090W, HIS3, HSP104, UBP6 and ARO8.<ref>PMID:11641273</ref> <ref>PMID:16179952</ref> <ref>PMID:16873066</ref> <ref>PMID:16437165</ref> <ref>PMID:17051211</ref> <ref>PMID:18812321</ref> <ref>PMID:20110468</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Transmembrane E3 ligases play crucial roles in homeostasis. Much protein and organelle quality control, and metabolic regulation, are determined by ER-resident MARCH6 E3 ligases, including Doa10 in yeast. Here, we present Doa10/MARCH6 structural analysis by cryo-EM and AlphaFold predictions, and a structure-based mutagenesis campaign. The majority of Doa10/MARCH6 adopts a unique circular structure within the membrane. This channel is established by a lipid-binding scaffold, and gated by a flexible helical bundle. The ubiquitylation active site is positioned over the channel by connections between the cytosolic E3 ligase RING domain and the membrane-spanning scaffold and gate. Here, by assaying 95 MARCH6 variants for effects on stability of the well-characterized substrate SQLE, which regulates cholesterol levels, we reveal crucial roles of the gated channel and RING domain consistent with AlphaFold-models of substrate-engaged and ubiquitylation complexes. SQLE degradation further depends on connections between the channel and RING domain, and lipid binding sites, revealing how interconnected Doa10/MARCH6 elements could orchestrate metabolic signals, substrate binding, and E3 ligase activity.

-	~~Authors~~:	+	Doa10/MARCH6 architecture interconnects E3 ligase activity with lipid-binding transmembrane channel to regulate SQLE.,Botsch JJ, Junker R, Sorgenfrei M, Ogger PP, Stier L, von Gronau S, Murray PJ, Seeger MA, Schulman BA, Brauning B Nat Commun. 2024 Jan 9;15(1):410. doi: 10.1038/s41467-023-44670-5. PMID:38195637<ref>PMID:38195637</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8pd0" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Saccharomyces cerevisiae]]
		+	[[Category: Botsch JJ]]
		+	[[Category: Braeuning B]]
		+	[[Category: Schulman BA]]

OCA at 04:48, 19 July 2023

OCA — Wed, 19 Jul 2023 04:48:43 GMT

←Older revision		Revision as of 04:48, 19 July 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8pd0 is ON HOLD	+	The entry 8pd0 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "8pd0" [edit=sysop:move=sysop]

OCA — Wed, 21 Jun 2023 08:22:33 GMT

Protected "8pd0" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:22, 21 June 2023

OCA: New page: '''Unreleased structure''' The entry 8pd0 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 21 Jun 2023 08:22:32 GMT

New page: '''Unreleased structure''' The entry 8pd0 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8pd0 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

8pd0 - Revision history

OCA at 10:07, 17 January 2024

OCA at 04:48, 19 July 2023

OCA: Protected "8pd0" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8pd0 is ON HOLD Authors: Description: Category: Unreleased Structures