7sd1 - Revision history

OCA at 16:49, 18 October 2023

2023-10-18T16:49:37Z

←Older revision		Revision as of 16:49, 18 October 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7sd1]] is a 4 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=7SD1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SD1 FirstGlance]. <br>		<table><tr><td colspan='2'>[[7sd1]] is a 4 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=7SD1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SD1 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=7sd1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sd1 OCA], [https://pdbe.org/7sd1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sd1 RCSB], [https://www.ebi.ac.uk/pdbsum/7sd1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sd1 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]] 3.19Å</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=7sd1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sd1 OCA], [https://pdbe.org/7sd1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sd1 RCSB], [https://www.ebi.ac.uk/pdbsum/7sd1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sd1 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/SHOC2_HUMAN SHOC2_HUMAN]] Noonan syndrome-like disorder with loose anagen hair. The disease is caused by variants affecting the gene represented in this entry.	+	[https://www.uniprot.org/uniprot/SHOC2_HUMAN SHOC2_HUMAN] Noonan syndrome-like disorder with loose anagen hair. The disease is caused by variants affecting the gene represented in this entry.
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/SHOC2_HUMAN SHOC2_HUMAN]] Regulatory subunit of protein phosphatase 1 (PP1c) that acts as a M-Ras/MRAS effector and participates in MAPK pathway activation. Upon M-Ras/MRAS activation, targets PP1c to specifically dephosphorylate the 'Ser-259' inhibitory site of RAF1 kinase and stimulate RAF1 activity at specialized signaling complexes.<ref>PMID:10783161</ref> <ref>PMID:16630891</ref> <ref>PMID:25137548</ref>	+	[https://www.uniprot.org/uniprot/SHOC2_HUMAN SHOC2_HUMAN] Regulatory subunit of protein phosphatase 1 (PP1c) that acts as a M-Ras/MRAS effector and participates in MAPK pathway activation. Upon M-Ras/MRAS activation, targets PP1c to specifically dephosphorylate the 'Ser-259' inhibitory site of RAF1 kinase and stimulate RAF1 activity at specialized signaling complexes.<ref>PMID:10783161</ref> <ref>PMID:16630891</ref> <ref>PMID:25137548</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 04:44, 8 September 2022

2022-09-08T04:44:55Z

←Older revision		Revision as of 04:44, 8 September 2022
Line 3:		Line 3:
	<StructureSection load='7sd1' size='340' side='right'caption='[[7sd1]], [[Resolution\|resolution]] 3.19Å' scene=''>		<StructureSection load='7sd1' size='340' side='right'caption='[[7sd1]], [[Resolution\|resolution]] 3.19Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7sd1]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SD1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SD1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7sd1]] is a 4 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=7SD1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SD1 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=7sd1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sd1 OCA], [https://pdbe.org/7sd1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sd1 RCSB], [https://www.ebi.ac.uk/pdbsum/7sd1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sd1 ProSAT]</span></td></tr>		</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=7sd1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sd1 OCA], [https://pdbe.org/7sd1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sd1 RCSB], [https://www.ebi.ac.uk/pdbsum/7sd1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sd1 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/SHOC2_HUMAN SHOC2_HUMAN]] Noonan syndrome-like disorder with loose anagen hair. The disease is caused by variants affecting the gene represented in this entry.	+	[[https://www.uniprot.org/uniprot/SHOC2_HUMAN SHOC2_HUMAN]] Noonan syndrome-like disorder with loose anagen hair. The disease is caused by variants affecting the gene represented in this entry.
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/SHOC2_HUMAN SHOC2_HUMAN]] Regulatory subunit of protein phosphatase 1 (PP1c) that acts as a M-Ras/MRAS effector and participates in MAPK pathway activation. Upon M-Ras/MRAS activation, targets PP1c to specifically dephosphorylate the 'Ser-259' inhibitory site of RAF1 kinase and stimulate RAF1 activity at specialized signaling complexes.<ref>PMID:10783161</ref> <ref>PMID:16630891</ref> <ref>PMID:25137548</ref>	+	[[https://www.uniprot.org/uniprot/SHOC2_HUMAN SHOC2_HUMAN]] Regulatory subunit of protein phosphatase 1 (PP1c) that acts as a M-Ras/MRAS effector and participates in MAPK pathway activation. Upon M-Ras/MRAS activation, targets PP1c to specifically dephosphorylate the 'Ser-259' inhibitory site of RAF1 kinase and stimulate RAF1 activity at specialized signaling complexes.<ref>PMID:10783161</ref> <ref>PMID:16630891</ref> <ref>PMID:25137548</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Hymowitz~~, S G~~]]	+	[[Category: Hymowitz SG]]
-	[[Category: Liau~~, N P.D~~]]	+	[[Category: Liau NPD]]
-	[[Category: Sudhamsu, J]]	+	[[Category: Sudhamsu J]]
-	~~[[Category: Pp1c]]~~	+
-	~~[[Category: Ra]]~~	+
-	~~[[Category: Scaffold]]~~	+
-	~~[[Category: Signaling protein~~]]	+

OCA at 18:17, 27 July 2022

2022-07-27T18:17:49Z

←Older revision		Revision as of 18:17, 27 July 2022
Line 10:		Line 10:
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/SHOC2_HUMAN SHOC2_HUMAN]] Regulatory subunit of protein phosphatase 1 (PP1c) that acts as a M-Ras/MRAS effector and participates in MAPK pathway activation. Upon M-Ras/MRAS activation, targets PP1c to specifically dephosphorylate the 'Ser-259' inhibitory site of RAF1 kinase and stimulate RAF1 activity at specialized signaling complexes.<ref>PMID:10783161</ref> <ref>PMID:16630891</ref> <ref>PMID:25137548</ref>		[[https://www.uniprot.org/uniprot/SHOC2_HUMAN SHOC2_HUMAN]] Regulatory subunit of protein phosphatase 1 (PP1c) that acts as a M-Ras/MRAS effector and participates in MAPK pathway activation. Upon M-Ras/MRAS activation, targets PP1c to specifically dephosphorylate the 'Ser-259' inhibitory site of RAF1 kinase and stimulate RAF1 activity at specialized signaling complexes.<ref>PMID:10783161</ref> <ref>PMID:16630891</ref> <ref>PMID:25137548</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The RAS-RAF pathway is one of the most commonly dysregulated in human cancers(1-3). Despite decades of study, understanding of the molecular mechanisms underlying dimerization and activation(4) of the kinase RAF remains limited. Recent structures of inactive RAF monomer(5) and active RAF dimer(5-8) bound to 14-3-3(9,10) have revealed the mechanisms by which 14-3-3 stabilizes both RAF conformations via specific phosphoserine residues. Prior to RAF dimerization, the protein phosphatase 1 catalytic subunit (PP1C) must dephosphorylate the N-terminal phosphoserine (NTpS) of RAF(11) to relieve inhibition by 14-3-3, although PP1C in isolation lacks intrinsic substrate selectivity. SHOC2 is as an essential scaffolding protein that engages both PP1C and RAS to dephosphorylate RAF NTpS(11-13), but the structure of SHOC2 and the architecture of the presumptive SHOC2-PP1C-RAS complex remain unknown. Here we present a cryo-electron microscopy structure of the SHOC2-PP1C-MRAS complex to an overall resolution of 3 A, revealing a tripartite molecular architecture in which a crescent-shaped SHOC2 acts as a cradle and brings together PP1C and MRAS. Our work demonstrates the GTP dependence of multiple RAS isoforms for complex formation, delineates the RAS-isoform preference for complex assembly, and uncovers how the SHOC2 scaffold and RAS collectively drive specificity of PP1C for RAF NTpS. Our data indicate that disease-relevant mutations affect complex assembly, reveal the simultaneous requirement of two RAS molecules for RAF activation, and establish rational avenues for discovery of new classes of inhibitors to target this pathway.
		+
		+	Structural basis for SHOC2 modulation of RAS signalling.,Liau NPD, Johnson MC, Izadi S, Gerosa L, Hammel M, Bruning JM, Wendorff TJ, Phung W, Hymowitz SG, Sudhamsu J Nature. 2022 Jun 29. pii: 10.1038/s41586-022-04838-3. doi:, 10.1038/s41586-022-04838-3. PMID:35768504<ref>PMID:35768504</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7sd1" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:11, 20 July 2022

2022-07-20T07:11:52Z

←Older revision		Revision as of 07:11, 20 July 2022
Line 1:		Line 1:

	==Crystal structure of SHOC2==		==Crystal structure of SHOC2==
-	<StructureSection load='7sd1' size='340' side='right'caption='[[7sd1]]' scene=''>	+	<StructureSection load='7sd1' size='340' side='right'caption='[[7sd1]], [[Resolution\|resolution]] 3.19Å' 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=7SD1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SD1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7sd1]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SD1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SD1 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=7sd1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sd1 OCA], [https://pdbe.org/7sd1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sd1 RCSB], [https://www.ebi.ac.uk/pdbsum/7sd1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sd1 ProSAT]</span></td></tr>		</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=7sd1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sd1 OCA], [https://pdbe.org/7sd1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sd1 RCSB], [https://www.ebi.ac.uk/pdbsum/7sd1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sd1 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[[https://www.uniprot.org/uniprot/SHOC2_HUMAN SHOC2_HUMAN]] Noonan syndrome-like disorder with loose anagen hair. The disease is caused by variants affecting the gene represented in this entry.
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/SHOC2_HUMAN SHOC2_HUMAN]] Regulatory subunit of protein phosphatase 1 (PP1c) that acts as a M-Ras/MRAS effector and participates in MAPK pathway activation. Upon M-Ras/MRAS activation, targets PP1c to specifically dephosphorylate the 'Ser-259' inhibitory site of RAF1 kinase and stimulate RAF1 activity at specialized signaling complexes.<ref>PMID:10783161</ref> <ref>PMID:16630891</ref> <ref>PMID:25137548</ref>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Hymowitz SG]]	+	[[Category: Hymowitz, S G]]
-	[[Category: Liau ~~NPD~~]]	+	[[Category: Liau, N P.D]]
-	[[Category: Sudhamsu J]]	+	[[Category: Sudhamsu, J]]
		+	[[Category: Pp1c]]
		+	[[Category: Ra]]
		+	[[Category: Scaffold]]
		+	[[Category: Signaling protein]]

OCA at 02:56, 21 April 2022

2022-04-21T02:56:12Z

←Older revision		Revision as of 02:56, 21 April 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7sd1 is ~~ON HOLD until Paper Publication~~	+	==Crystal structure of SHOC2==
-		+	<StructureSection load='7sd1' size='340' side='right'caption='[[7sd1]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SD1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SD1 FirstGlance]. <br>
-	~~Description~~:	+	</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=7sd1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sd1 OCA], [https://pdbe.org/7sd1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sd1 RCSB], [https://www.ebi.ac.uk/pdbsum/7sd1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sd1 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Hymowitz SG]]
		+	[[Category: Liau NPD]]
		+	[[Category: Sudhamsu J]]

OCA at 15:05, 20 October 2021

2021-10-20T15:05:22Z

←Older revision		Revision as of 15:05, 20 October 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7sd1 is ON HOLD	+	The entry 7sd1 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7sd1" [edit=sysop:move=sysop]

2021-10-06T04:17:08Z

Protected "7sd1" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:17, 6 October 2021

OCA: New page: '''Unreleased structure''' The entry 7sd1 is ON HOLD Authors: Description: Category: Unreleased Structures

2021-10-06T04:17:06Z

New page: '''Unreleased structure''' The entry 7sd1 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7sd1 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]