7t1y - Revision history

OCA at 16:57, 18 October 2023

OCA — Wed, 18 Oct 2023 16:57:56 GMT

←Older revision		Revision as of 16:57, 18 October 2023
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-	====	+	==Structure of the Fbw7-Skp1-MycCdegron complex==
-	<StructureSection load='7t1y' size='340' side='right'caption='[[7t1y]]' scene=''>	+	<StructureSection load='7t1y' size='340' side='right'caption='[[7t1y]], [[Resolution\|resolution]] 2.55Å' 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'>[[7t1y]] is a 3 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=7T1Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7T1Y 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=7t1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t1y OCA], [https://pdbe.org/7t1y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t1y RCSB], [https://www.ebi.ac.uk/pdbsum/7t1y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t1y 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]] 2.55Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=7t1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t1y OCA], [https://pdbe.org/7t1y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t1y RCSB], [https://www.ebi.ac.uk/pdbsum/7t1y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t1y ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/SKP1_HUMAN SKP1_HUMAN] Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(Cyclin F) directs ubiquitination of CP110.<ref>PMID:16209941</ref> <ref>PMID:20181953</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	c-Myc (hereafter, Myc) is a cancer driver whose abundance is regulated by the SCF(Fbw7) ubiquitin ligase and proteasomal degradation. Fbw7 binds to a phosphorylated Myc degron centered at threonine 58 (T58), and mutations of Fbw7 or T58 impair Myc degradation in cancers. Here, we identify a second Fbw7 phosphodegron at Myc T244 that is required for Myc ubiquitylation and acts in concert with T58 to engage Fbw7. While Ras-dependent Myc serine 62 phosphorylation (pS62) is thought to stabilize Myc by preventing Fbw7 binding, we find instead that pS62 greatly enhances Fbw7 binding and is an integral part of a high-affinity degron. Crystallographic studies revealed that both degrons bind Fbw7 in their diphosphorylated forms and that the T244 degron is recognized via a unique mode involving Fbw7 arginine 689 (R689), a mutational hotspot in cancers. These insights have important implications for Myc-associated tumorigenesis and therapeutic strategies targeting Myc stability.
		+
		+	Two diphosphorylated degrons control c-Myc degradation by the Fbw7 tumor suppressor.,Welcker M, Wang B, Rusnac DV, Hussaini Y, Swanger J, Zheng N, Clurman BE Sci Adv. 2022 Jan 28;8(4):eabl7872. doi: 10.1126/sciadv.abl7872. Epub 2022 Jan , 28. PMID:35089787<ref>PMID:35089787</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7t1y" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Clurman BE]]
		+	[[Category: Rusnac DV]]
		+	[[Category: Wang B]]
		+	[[Category: Zheng N]]

OCA at 10:18, 16 February 2022

OCA — Wed, 16 Feb 2022 10:18:26 GMT

←Older revision		Revision as of 10:18, 16 February 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7t1y ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7t1y' size='340' side='right'caption='[[7t1y]]' scene=''>
-	~~Authors~~: ~~Wang, B~~.~~, Rusnac, D~~.V.~~, Clurman, B~~.E.~~, Zheng, N~~.	+	== 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~~: ~~Structure of the Fbw7-Skp1-MycCdegron 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=7t1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t1y OCA], [https://pdbe.org/7t1y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t1y RCSB], [https://www.ebi.ac.uk/pdbsum/7t1y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t1y ProSAT]</span></td></tr>
-	[~~[Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[~~[Category~~: ~~Rusnac~~, D.V]]	+	__TOC__
-	[~~[Category~~: ~~Wang~~, B]]	+	</StructureSection>
-	[[Category: ~~Clurman, B.E~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Zheng, N~~]]	+	[[Category: Z-disk]]

OCA at 08:34, 12 January 2022

OCA — Wed, 12 Jan 2022 08:34:32 GMT

←Older revision		Revision as of 08:34, 12 January 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7t1y is ON HOLD	+	The entry 7t1y is ON HOLD until Paper Publication

	Authors: Wang, B., Rusnac, D.V., Clurman, B.E., Zheng, N.		Authors: Wang, B., Rusnac, D.V., Clurman, B.E., Zheng, N.

OCA at 14:03, 22 December 2021

OCA — Wed, 22 Dec 2021 14:03:23 GMT

←Older revision		Revision as of 14:03, 22 December 2021
Line 3:		Line 3:
	The entry 7t1y is ON HOLD		The entry 7t1y is ON HOLD

-	Authors: Wang, B., Rusnac, D.V~~., Zheng, N~~., Clurman, B.E.	+	Authors: Wang, B., Rusnac, D.V., Clurman, B.E., Zheng, N.

-	Description: Fbw7/Skp1 ~~in complex with Myc C~~-~~terminal degron~~	+	Description: Structure of the Fbw7-Skp1-MycCdegron complex
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Rusnac, D.V]]		[[Category: Rusnac, D.V]]

OCA: Protected "7t1y" [edit=sysop:move=sysop]

OCA — Wed, 08 Dec 2021 08:40:05 GMT

Protected "7t1y" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:40, 8 December 2021

OCA: New page: '''Unreleased structure''' The entry 7t1y is ON HOLD Authors: Wang, B., Rusnac, D.V., Zheng, N., Clurman, B.E. Description: Fbw7/Skp1 in complex with Myc C-terminal degron [[Category: ...

OCA — Wed, 08 Dec 2021 08:40:03 GMT

New page: '''Unreleased structure''' The entry 7t1y is ON HOLD Authors: Wang, B., Rusnac, D.V., Zheng, N., Clurman, B.E. Description: Fbw7/Skp1 in complex with Myc C-terminal degron [[Category: ...

New page

'''Unreleased structure'''

The entry 7t1y is ON HOLD

Authors: Wang, B., Rusnac, D.V., Zheng, N., Clurman, B.E.

Description: Fbw7/Skp1 in complex with Myc C-terminal degron
[[Category: Unreleased Structures]]
[[Category: Rusnac, D.V]]
[[Category: Wang, B]]
[[Category: Clurman, B.E]]
[[Category: Zheng, N]]