7roy - Revision history

OCA at 10:41, 22 May 2024

2024-05-22T10:41:36Z

← Older revision		Revision as of 10:41, 22 May 2024
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	====		==The structure of the Fem1B:FNIP1 complex==
	<StructureSection load='7roy' size='340' side='right'caption='[[7roy]]' scene=''>		<StructureSection load='7roy' size='340' side='right'caption='[[7roy]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>		<table><tr><td colspan='2'>[[7roy]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ROY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ROY FirstGlance]. <br>
	</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=7roy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7roy OCA], [https://pdbe.org/7roy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7roy RCSB], [https://www.ebi.ac.uk/pdbsum/7roy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7roy ProSAT]</span></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]] 2.9Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7roy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7roy OCA], [https://pdbe.org/7roy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7roy RCSB], [https://www.ebi.ac.uk/pdbsum/7roy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7roy ProSAT]</span></td></tr>
	</table>		</table>
			== Function ==
			[https://www.uniprot.org/uniprot/FEM1B_MOUSE FEM1B_MOUSE] Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation (By similarity). The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms (By similarity). The CRL2(FEM1B) complex specifically recognizes proteins ending with -Gly-Leu-Asp-Arg, such as CDK5R1, leading to their ubiquitination and degradation (By similarity). Also acts as a regulator of the reductive stress response by mediating ubiquitination of reduced FNIP1: in response to reductive stress, the CRL2(FEM1B) complex specifically recognizes a conserved Cys degron in FNIP1 when this degron is reduced, leading to FNIP1 degradation and subsequent activation of mitochondria to recalibrate reactive oxygen species (ROS) (PubMed:32941802). Promotes ubiquitination of GLI1, suppressing GLI1 transcriptional activator activity (By similarity). Promotes ubiquitination and degradation of ANKRD37 (PubMed:21723927). Promotes ubiquitination and degradation of SLBP (By similarity). Involved in apoptosis by acting as a death receptor-associated protein that mediates apoptosis (By similarity). Also involved in glucose homeostasis in pancreatic islet (PubMed:16024793). May also act as an adapter/mediator in replication stress-induced signaling that leads to the activation of CHEK1 (By similarity).[UniProtKB:Q9UK73]<ref>PMID:16024793</ref> <ref>PMID:21723927</ref> <ref>PMID:32941802</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Although oxidative phosphorylation is best known for producing ATP, it also yields reactive oxygen species (ROS) as invariant byproducts. Depletion of ROS below their physiological levels, a phenomenon known as reductive stress, impedes cellular signaling and has been linked to cancer, diabetes, and cardiomyopathy. Cells alleviate reductive stress by ubiquitylating and degrading the mitochondrial gatekeeper FNIP1, yet it is unknown how the responsible E3 ligase CUL2(FEM1B) can bind its target based on redox state and how this is adjusted to changing cellular environments. Here, we show that CUL2(FEM1B) relies on zinc as a molecular glue to selectively recruit reduced FNIP1 during reductive stress. FNIP1 ubiquitylation is gated by pseudosubstrate inhibitors of the BEX family, which prevent premature FNIP1 degradation to protect cells from unwarranted ROS accumulation. FEM1B gain-of-function mutation and BEX deletion elicit similar developmental syndromes, showing that the zinc-dependent reductive stress response must be tightly regulated to maintain cellular and organismal homeostasis.

			Structural basis and regulation of the reductive stress response.,Manford AG, Mena EL, Shih KY, Gee CL, McMinimy R, Martinez-Gonzalez B, Sherriff R, Lew B, Zoltek M, Rodriguez-Perez F, Woldesenbet M, Kuriyan J, Rape M Cell. 2021 Oct 14;184(21):5375-5390.e16. doi: 10.1016/j.cell.2021.09.002. Epub , 2021 Sep 24. PMID:34562363<ref>PMID:34562363</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 7roy" style="background-color:#fffaf0;"></div>
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: ~~Z-disk~~]]		[[Category: Mus musculus]]
			[[Category: Gee CL]]
			[[Category: Manford AG]]
			[[Category: Mena EL]]
			[[Category: Rape M]]

OCA at 11:46, 13 October 2021

2021-10-13T11:46:41Z

← Older revision		Revision as of 11:46, 13 October 2021
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	~~'''Unreleased structure'''~~

	~~The entry~~ 7roy ~~is ON HOLD until Paper Publication~~		====
			<StructureSection load='7roy' size='340' side='right'caption='[[7roy]]' scene=''>
	~~Authors~~: ~~Gee, C~~.L.~~, Mena, E~~.L.~~, Manford, A~~.G.~~, Rape, M~~.		== Structural highlights ==
			<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
	~~Description~~: ~~The structure of the Fem1B~~:~~FNIP1 complex~~		</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=7roy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7roy OCA], [https://pdbe.org/7roy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7roy RCSB], [https://www.ebi.ac.uk/pdbsum/7roy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7roy ProSAT]</span></td></tr>
	[[~~Category~~: ~~Unreleased Structures~~]]		</table>
	[~~[Category~~: ~~Gee, C~~.L]]		__TOC__
	[~~[Category~~: ~~Manford, A~~.G]]		</StructureSection>
	[[Category: ~~Mena, E.L~~]]		[[Category: Large Structures]]
	[[Category: ~~Rape, M~~]]		[[Category: Z-disk]]

OCA at 07:43, 8 September 2021

2021-09-08T07:43:15Z

← Older revision		Revision as of 07:43, 8 September 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 7roy is ON HOLD		The entry 7roy is ON HOLD until Paper Publication

	Authors: Gee, C.L., Mena, E.L., Manford, A.G., Rape, M.		Authors: Gee, C.L., Mena, E.L., Manford, A.G., Rape, M.
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	Description: The structure of the Fem1B:FNIP1 complex		Description: The structure of the Fem1B:FNIP1 complex
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	~~[[Category: Mena, E.L]]~~
	[[Category: Gee, C.L]]		[[Category: Gee, C.L]]
	[[Category: Manford, A.G]]		[[Category: Manford, A.G]]
			[[Category: Mena, E.L]]
	[[Category: Rape, M]]		[[Category: Rape, M]]

OCA: Protected "7roy" [edit=sysop:move=sysop]

2021-08-11T05:11:51Z

Protected "7roy" [edit=sysop:move=sysop]

← Older revision	Revision as of 05:11, 11 August 2021
(No difference)

OCA: New page: '''Unreleased structure''' The entry 7roy is ON HOLD Authors: Gee, C.L., Mena, E.L., Manford, A.G., Rape, M. Description: The structure of the Fem1B:FNIP1 complex [[Category: Unrelease...

2021-08-11T05:11:50Z

New page: '''Unreleased structure''' The entry 7roy is ON HOLD Authors: Gee, C.L., Mena, E.L., Manford, A.G., Rape, M. Description: The structure of the Fem1B:FNIP1 complex [[Category: Unrelease...

New page

'''Unreleased structure'''

The entry 7roy is ON HOLD

Authors: Gee, C.L., Mena, E.L., Manford, A.G., Rape, M.

Description: The structure of the Fem1B:FNIP1 complex
[[Category: Unreleased Structures]]
[[Category: Mena, E.L]]
[[Category: Gee, C.L]]
[[Category: Manford, A.G]]
[[Category: Rape, M]]