7moc - Revision history

OCA at 19:40, 29 May 2024

2024-05-29T19:40:16Z

←Older revision		Revision as of 19:40, 29 May 2024
Line 3:		Line 3:
	<StructureSection load='7moc' size='340' side='right'caption='[[7moc]], [[Resolution\|resolution]] 4.56Å' scene=''>		<StructureSection load='7moc' size='340' side='right'caption='[[7moc]], [[Resolution\|resolution]] 4.56Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>~~[[7moc]] is a 2 chain structure.~~ Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MOC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MOC FirstGlance]. <br>	+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MOC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MOC 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=7moc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7moc OCA], [https://pdbe.org/7moc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7moc RCSB], [https://www.ebi.ac.uk/pdbsum/7moc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7moc ProSAT]</span></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 4.56Å</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=7moc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7moc OCA], [https://pdbe.org/7moc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7moc RCSB], [https://www.ebi.ac.uk/pdbsum/7moc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7moc ProSAT]</span></td></tr>
	</table>		</table>
-	== Disease ==
-	[[https://www.uniprot.org/uniprot/NF1_HUMAN NF1_HUMAN]] Defects in NF1 are the cause of neurofibromatosis type 1 (NF1) [MIM:[https://omim.org/entry/162200 162200]]; also known as von Recklinghausen syndrome. A disease characterized by patches of skin pigmentation (cafe-au-lait spots), Lisch nodules of the iris, tumors in the peripheral nervous system and fibromatous skin tumors. Individuals with the disorder have increased susceptibility to the development of benign and malignant tumors.<ref>PMID:2114220</ref> <ref>PMID:1302608</ref> <ref>PMID:7981679</ref> <ref>PMID:8081387</ref> <ref>PMID:8544190</ref> <ref>PMID:8834249</ref> <ref>PMID:8807336</ref> <ref>PMID:9003501</ref> <ref>PMID:9150739</ref> <ref>PMID:9101300</ref> <ref>PMID:9298829</ref> <ref>PMID:9668168</ref> <ref>PMID:10336779</ref> <ref>PMID:11258625</ref> <ref>PMID:10220149</ref> <ref>PMID:10712197</ref> <ref>PMID:10607834</ref> <ref>PMID:10980545</ref> <ref>PMID:11735023</ref> <ref>PMID:11857752</ref> <ref>PMID:12522551</ref> <ref>PMID:12552569</ref> <ref>PMID:12746402</ref> <ref>PMID:15523642</ref> <ref>PMID:15146469</ref> <ref>PMID:15060124</ref> <ref>PMID:15520408</ref> <ref>PMID:15948193</ref> <ref>PMID:21838856</ref> Defects in NF1 are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:[https://omim.org/entry/607785 607785]]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. Germline mutations of NF1 account for the association of JMML with type 1 neurofibromatosis (NF1). Defects in NF1 are the cause of Watson syndrome (WS) [MIM:[https://omim.org/entry/193520 193520]]. WS is characterized by the presence of pulmonary stenosis, cafe-au-lait spots, and mental retardation. WS is considered as an atypical form of NF1. Defects in NF1 are a cause of familial spinal neurofibromatosis (FSNF) [MIM:[https://omim.org/entry/162210 162210]]. Familial spinal NF is considered to be an alternative form of neurofibromatosis, showing multiple spinal tumors.<ref>PMID:11704931</ref> Defects in NF1 are a cause of neurofibromatosis-Noonan syndrome (NFNS) [MIM:[https://omim.org/entry/601321 601321]]. NFNS is characterized by manifestations of both NF1 and Noonan syndrome (NS). NS is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis.<ref>PMID:12707950</ref> <ref>PMID:16380919</ref> <ref>PMID:19845691</ref> Defects in NF1 may be a cause of colorectal cancer (CRC) [MIM:[https://omim.org/entry/114500 114500]].
-	== Function ==
-	[[https://www.uniprot.org/uniprot/NF1_HUMAN NF1_HUMAN]] Stimulates the GTPase activity of Ras. NF1 shows greater affinity for Ras GAP, but lower specific activity. May be a regulator of Ras activity.<ref>PMID:2121371</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Neurofibromin (NF1) mutations cause neurofibromatosis type 1 and drive numerous cancers, including breast and brain tumors. NF1 inhibits cellular proliferation through its guanosine triphosphatase-activating protein (GAP) activity against rat sarcoma (RAS). In the present study, cryo-electron microscope studies reveal that the human ~640-kDa NF1 homodimer features a gigantic 30 x 10 nm array of alpha-helices that form a core lemniscate-shaped scaffold. Three-dimensional variability analysis captured the catalytic GAP-related domain and lipid-binding SEC-PH domains positioned against the core scaffold in a closed, autoinhibited conformation. We postulate that interaction with the plasma membrane may release the closed conformation to promote RAS inactivation. Our structural data further allow us to map the location of disease-associated NF1 variants and provide a long-sought-after structural explanation for the extreme susceptibility of the molecule to loss-of-function mutations. Collectively these findings present potential new routes for therapeutic modulation of the RAS pathway.

-	The cryo-EM structure of the human neurofibromin dimer reveals the molecular basis for neurofibromatosis type 1.,Lupton CJ, Bayly-Jones C, D'Andrea L, Huang C, Schittenhelm RB, Venugopal H, Whisstock JC, Halls ML, Ellisdon AM Nat Struct Mol Biol. 2021 Dec;28(12):982-988. doi: 10.1038/s41594-021-00687-2., Epub 2021 Dec 9. PMID:34887559<ref>PMID:34887559</ref>	+	==See Also==
-		+	*[[Neurofibromin\|Neurofibromin]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 7moc" style="background-color:#fffaf0;"></div>~~	+
-	== ~~References~~ ==	+
-	~~<references/>~~	+
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bayly-Jones, C]]	+	[[Category: Bayly-Jones C]]
-	~~[[Category: Ellisdon, A M~~]]	+	[[Category: Lupton CJ]]
-	[[Category: Lupton~~, C J]]~~	+
-	~~[[Category: Antitumor protein]]~~	+
-	~~[[Category: Autoinhibition]]~~	+
-	~~[[Category: Heat repeat]]~~	+
-	~~[[Category: Ras-gap]]~~	+
-	~~[[Category: Scaffold~~]]	+

OCA at 07:17, 16 March 2022

2022-03-16T07:17:45Z

←Older revision		Revision as of 07:17, 16 March 2022
Line 25:		Line 25:
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Bayly-Jones, C]]		[[Category: Bayly-Jones, C]]
		+	[[Category: Ellisdon, A M]]
	[[Category: Lupton, C J]]		[[Category: Lupton, C J]]
	[[Category: Antitumor protein]]		[[Category: Antitumor protein]]

OCA at 14:16, 29 December 2021

2021-12-29T14:16:45Z

←Older revision		Revision as of 14:16, 29 December 2021
Line 1:		Line 1:

	==Neurofibromin core==		==Neurofibromin core==
-	<StructureSection load='7moc' size='340' side='right'caption='[[7moc]]' scene=''>	+	<StructureSection load='7moc' size='340' side='right'caption='[[7moc]], [[Resolution\|resolution]] 4.56Å' 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=7MOC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MOC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7moc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MOC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MOC 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=7moc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7moc OCA], [https://pdbe.org/7moc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7moc RCSB], [https://www.ebi.ac.uk/pdbsum/7moc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7moc 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=7moc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7moc OCA], [https://pdbe.org/7moc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7moc RCSB], [https://www.ebi.ac.uk/pdbsum/7moc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7moc ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[[https://www.uniprot.org/uniprot/NF1_HUMAN NF1_HUMAN]] Defects in NF1 are the cause of neurofibromatosis type 1 (NF1) [MIM:[https://omim.org/entry/162200 162200]]; also known as von Recklinghausen syndrome. A disease characterized by patches of skin pigmentation (cafe-au-lait spots), Lisch nodules of the iris, tumors in the peripheral nervous system and fibromatous skin tumors. Individuals with the disorder have increased susceptibility to the development of benign and malignant tumors.<ref>PMID:2114220</ref> <ref>PMID:1302608</ref> <ref>PMID:7981679</ref> <ref>PMID:8081387</ref> <ref>PMID:8544190</ref> <ref>PMID:8834249</ref> <ref>PMID:8807336</ref> <ref>PMID:9003501</ref> <ref>PMID:9150739</ref> <ref>PMID:9101300</ref> <ref>PMID:9298829</ref> <ref>PMID:9668168</ref> <ref>PMID:10336779</ref> <ref>PMID:11258625</ref> <ref>PMID:10220149</ref> <ref>PMID:10712197</ref> <ref>PMID:10607834</ref> <ref>PMID:10980545</ref> <ref>PMID:11735023</ref> <ref>PMID:11857752</ref> <ref>PMID:12522551</ref> <ref>PMID:12552569</ref> <ref>PMID:12746402</ref> <ref>PMID:15523642</ref> <ref>PMID:15146469</ref> <ref>PMID:15060124</ref> <ref>PMID:15520408</ref> <ref>PMID:15948193</ref> <ref>PMID:21838856</ref> Defects in NF1 are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:[https://omim.org/entry/607785 607785]]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. Germline mutations of NF1 account for the association of JMML with type 1 neurofibromatosis (NF1). Defects in NF1 are the cause of Watson syndrome (WS) [MIM:[https://omim.org/entry/193520 193520]]. WS is characterized by the presence of pulmonary stenosis, cafe-au-lait spots, and mental retardation. WS is considered as an atypical form of NF1. Defects in NF1 are a cause of familial spinal neurofibromatosis (FSNF) [MIM:[https://omim.org/entry/162210 162210]]. Familial spinal NF is considered to be an alternative form of neurofibromatosis, showing multiple spinal tumors.<ref>PMID:11704931</ref> Defects in NF1 are a cause of neurofibromatosis-Noonan syndrome (NFNS) [MIM:[https://omim.org/entry/601321 601321]]. NFNS is characterized by manifestations of both NF1 and Noonan syndrome (NS). NS is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis.<ref>PMID:12707950</ref> <ref>PMID:16380919</ref> <ref>PMID:19845691</ref> Defects in NF1 may be a cause of colorectal cancer (CRC) [MIM:[https://omim.org/entry/114500 114500]].
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/NF1_HUMAN NF1_HUMAN]] Stimulates the GTPase activity of Ras. NF1 shows greater affinity for Ras GAP, but lower specific activity. May be a regulator of Ras activity.<ref>PMID:2121371</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Neurofibromin (NF1) mutations cause neurofibromatosis type 1 and drive numerous cancers, including breast and brain tumors. NF1 inhibits cellular proliferation through its guanosine triphosphatase-activating protein (GAP) activity against rat sarcoma (RAS). In the present study, cryo-electron microscope studies reveal that the human ~640-kDa NF1 homodimer features a gigantic 30 x 10 nm array of alpha-helices that form a core lemniscate-shaped scaffold. Three-dimensional variability analysis captured the catalytic GAP-related domain and lipid-binding SEC-PH domains positioned against the core scaffold in a closed, autoinhibited conformation. We postulate that interaction with the plasma membrane may release the closed conformation to promote RAS inactivation. Our structural data further allow us to map the location of disease-associated NF1 variants and provide a long-sought-after structural explanation for the extreme susceptibility of the molecule to loss-of-function mutations. Collectively these findings present potential new routes for therapeutic modulation of the RAS pathway.
		+
		+	The cryo-EM structure of the human neurofibromin dimer reveals the molecular basis for neurofibromatosis type 1.,Lupton CJ, Bayly-Jones C, D'Andrea L, Huang C, Schittenhelm RB, Venugopal H, Whisstock JC, Halls ML, Ellisdon AM Nat Struct Mol Biol. 2021 Dec;28(12):982-988. doi: 10.1038/s41594-021-00687-2., Epub 2021 Dec 9. PMID:34887559<ref>PMID:34887559</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7moc" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bayly-Jones C]]	+	[[Category: Bayly-Jones, C]]
-	[[Category: Lupton CJ]]	+	[[Category: Lupton, C J]]
		+	[[Category: Antitumor protein]]
		+	[[Category: Autoinhibition]]
		+	[[Category: Heat repeat]]
		+	[[Category: Ras-gap]]
		+	[[Category: Scaffold]]

OCA at 16:48, 15 December 2021

2021-12-15T16:48:19Z

←Older revision		Revision as of 16:48, 15 December 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

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

OCA at 05:07, 25 August 2021

2021-08-25T05:07:25Z

←Older revision		Revision as of 05:07, 25 August 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7moc is ON HOLD ~~until Paper Publication~~	+	The entry 7moc is ON HOLD

	Authors: Lupton, C.J., Bayly-Jones, C.		Authors: Lupton, C.J., Bayly-Jones, C.

-	Description: Neurofibromin ~~single lobe~~ core	+	Description: Neurofibromin core
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Bayly-Jones, C]]		[[Category: Bayly-Jones, C]]
	[[Category: Lupton, C.J]]		[[Category: Lupton, C.J]]

OCA at 11:04, 9 June 2021

2021-06-09T11:04:30Z

←Older revision		Revision as of 11:04, 9 June 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Lupton, C.J., Bayly-Jones, C.		Authors: Lupton, C.J., Bayly-Jones, C.

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

2021-05-12T08:13:12Z

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

←Older revision

Revision as of 08:13, 12 May 2021

OCA: New page: '''Unreleased structure''' The entry 7moc is ON HOLD Authors: Lupton, C.J., Bayly-Jones, C. Description: Neurofibromin single lobe core Category: Unreleased Structures [[Category: ...

2021-05-12T08:13:11Z

New page: '''Unreleased structure''' The entry 7moc is ON HOLD Authors: Lupton, C.J., Bayly-Jones, C. Description: Neurofibromin single lobe core Category: Unreleased Structures [[Category: ...

New page

'''Unreleased structure'''

The entry 7moc is ON HOLD

Authors: Lupton, C.J., Bayly-Jones, C.

Description: Neurofibromin single lobe core
[[Category: Unreleased Structures]]
[[Category: Bayly-Jones, C]]
[[Category: Lupton, C.J]]