5fn3 - Revision history

OCA at 06:58, 19 July 2023

2023-07-19T06:58:52Z

←Older revision		Revision as of 06:58, 19 July 2023
Line 3:		Line 3:
	<SX load='5fn3' size='340' side='right' viewer='molstar' caption='[[5fn3]], [[Resolution\|resolution]] 4.10Å' scene=''>		<SX load='5fn3' size='340' side='right' viewer='molstar' caption='[[5fn3]], [[Resolution\|resolution]] 4.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5fn3]] is a 5 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FN3 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5FN3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5fn3]] is a 5 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=5FN3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FN3 FirstGlance]. <br>
-	</td></tr><tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~>[[5fn2\|5fn2]], [[5fn4\|5fn4]], [[5fn5\|5fn5]]</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]] 4.1Å</td></tr>
-	~~<tr~~ id~~='gene'><td class~~="~~sblockLbl~~">~~<b>~~[[~~Gene~~\|~~Gene:~~]]~~</b></td><td class="sblockDat">NCSTN, KIAA0253, UNQ1874/PRO4317 ([http://www~~.~~ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info~~&srchmode=5&id=9606 HUMAN]), PSEN1, AD3, PS1, PSNL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), APH1A, PSF, CGI-78, UNQ579/PRO1141 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PSENEN, PEN2, MDS033 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5fn3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fn3 OCA], [https://pdbe.org/5fn3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fn3 RCSB], [https://www.ebi.ac.uk/pdbsum/5fn3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fn3 ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5fn3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fn3 OCA], [~~http~~://pdbe.org/5fn3 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5fn3 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5fn3 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5fn3 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[[http://www.uniprot.org/uniprot/PEN2_HUMAN PEN2_HUMAN]] Hidradenitis suppurativa. The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/NICA_HUMAN NICA_HUMAN]] Hidradenitis suppurativa. The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/PSN1_HUMAN PSN1_HUMAN]] Defects in PSEN1 are a cause of Alzheimer disease type 3 (AD3) [MIM:[~~http~~://omim.org/entry/607822 607822]]. AD3 is a familial early-onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death.<ref>PMID:12058025</ref> <ref>PMID:7596406</ref> <ref>PMID:8634711</ref> <ref>PMID:8634712</ref> <ref>PMID:7651536</ref> <ref>PMID:7550356</ref> <ref>PMID:8733303</ref> <ref>PMID:9225696</ref> <ref>PMID:9298817</ref> <ref>PMID:9172170</ref> <ref>PMID:9833068</ref> <ref>PMID:9384602</ref> <ref>PMID:9521423</ref> <ref>PMID:10200054</ref> <ref>PMID:9719376</ref> <ref>PMID:9507958</ref> <ref>PMID:9831473</ref> <ref>PMID:10441572</ref> <ref>PMID:10090481</ref> <ref>PMID:10447269</ref> <ref>PMID:10533070</ref> <ref>PMID:10025789</ref> <ref>PMID:10208579</ref> <ref>PMID:10439444</ref> <ref>PMID:10631141</ref> <ref>PMID:10644793</ref> <ref>PMID:11027672</ref> [:]<ref>PMID:11710891</ref> <ref>PMID:11920851</ref> <ref>PMID:12048239</ref> <ref>PMID:12484344</ref> <ref>PMID:12493737</ref> Defects in PSEN1 are a cause of frontotemporal dementia (FTD) [MIM:[~~http~~://omim.org/entry/600274 600274]]. Defects in PSEN1 are the cause of cardiomyopathy dilated type 1U (CMD1U) [MIM:[~~http~~://omim.org/entry/613694 613694]]. It is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.<ref>PMID:17186461</ref> Defects in PSEN1 are the cause of familial acne inversa type 3 (ACNINV3) [MIM:[~~http~~://omim.org/entry/613737 613737]]. A chronic relapsing inflammatory disease of the hair follicles characterized by recurrent draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty.<ref>PMID:20929727</ref>	+	[https://www.uniprot.org/uniprot/PSN1_HUMAN PSN1_HUMAN] Defects in PSEN1 are a cause of Alzheimer disease type 3 (AD3) [MIM:[https://omim.org/entry/607822 607822]. AD3 is a familial early-onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death.<ref>PMID:12058025</ref> <ref>PMID:7596406</ref> <ref>PMID:8634711</ref> <ref>PMID:8634712</ref> <ref>PMID:7651536</ref> <ref>PMID:7550356</ref> <ref>PMID:8733303</ref> <ref>PMID:9225696</ref> <ref>PMID:9298817</ref> <ref>PMID:9172170</ref> <ref>PMID:9833068</ref> <ref>PMID:9384602</ref> <ref>PMID:9521423</ref> <ref>PMID:10200054</ref> <ref>PMID:9719376</ref> <ref>PMID:9507958</ref> <ref>PMID:9831473</ref> <ref>PMID:10441572</ref> <ref>PMID:10090481</ref> <ref>PMID:10447269</ref> <ref>PMID:10533070</ref> <ref>PMID:10025789</ref> <ref>PMID:10208579</ref> <ref>PMID:10439444</ref> <ref>PMID:10631141</ref> <ref>PMID:10644793</ref> <ref>PMID:11027672</ref> [:]<ref>PMID:11710891</ref> <ref>PMID:11920851</ref> <ref>PMID:12048239</ref> <ref>PMID:12484344</ref> <ref>PMID:12493737</ref> Defects in PSEN1 are a cause of frontotemporal dementia (FTD) [MIM:[https://omim.org/entry/600274 600274]. Defects in PSEN1 are the cause of cardiomyopathy dilated type 1U (CMD1U) [MIM:[https://omim.org/entry/613694 613694]. It is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.<ref>PMID:17186461</ref> Defects in PSEN1 are the cause of familial acne inversa type 3 (ACNINV3) [MIM:[https://omim.org/entry/613737 613737]. A chronic relapsing inflammatory disease of the hair follicles characterized by recurrent draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty.<ref>PMID:20929727</ref>
	== Function ==		== Function ==
-	[[http://www.uniprot.org/uniprot/PEN2_HUMAN PEN2_HUMAN]] Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (beta-amyloid precursor protein). Probably represents the last step of maturation of gamma-secretase, facilitating endoproteolysis of presenilin and conferring gamma-secretase activity.<ref>PMID:12522139</ref> <ref>PMID:12763021</ref> [[http://www.uniprot.org/uniprot/NICA_HUMAN NICA_HUMAN]] Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (beta-amyloid precursor protein). It probably represents a stabilizing cofactor required for the assembly of the gamma-secretase complex. [[http://www.uniprot.org/uniprot/APH1A_HUMAN APH1A_HUMAN]] Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors and APP (beta-amyloid precursor protein). It probably represents a stabilizing cofactor for the presenilin homodimer that promotes the formation of a stable complex.<ref>PMID:12297508</ref> <ref>PMID:12522139</ref> <ref>PMID:12763021</ref> [[http://www.uniprot.org/uniprot/PSN1_HUMAN PSN1_HUMAN]] Probable catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (beta-amyloid precursor protein). Requires the other members of the gamma-secretase complex to have a protease activity. May play a role in intracellular signaling and gene expression or in linking chromatin to the nuclear membrane. Stimulates cell-cell adhesion though its association with the E-cadherin/catenin complex. Under conditions of apoptosis or calcium influx, cleaves E-cadherin promoting the disassembly of the E-cadherin/catenin complex and increasing the pool of cytoplasmic beta-catenin, thus negatively regulating Wnt signaling. May also play a role in hematopoiesis.<ref>PMID:10545183</ref> <ref>PMID:10593990</ref> <ref>PMID:10206644</ref> <ref>PMID:10899933</ref> <ref>PMID:10811883</ref> <ref>PMID:11226248</ref> <ref>PMID:15341515</ref> <ref>PMID:16305624</ref>	+	[https://www.uniprot.org/uniprot/PSN1_HUMAN PSN1_HUMAN] Probable catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (beta-amyloid precursor protein). Requires the other members of the gamma-secretase complex to have a protease activity. May play a role in intracellular signaling and gene expression or in linking chromatin to the nuclear membrane. Stimulates cell-cell adhesion though its association with the E-cadherin/catenin complex. Under conditions of apoptosis or calcium influx, cleaves E-cadherin promoting the disassembly of the E-cadherin/catenin complex and increasing the pool of cytoplasmic beta-catenin, thus negatively regulating Wnt signaling. May also play a role in hematopoiesis.<ref>PMID:10545183</ref> <ref>PMID:10593990</ref> <ref>PMID:10206644</ref> <ref>PMID:10899933</ref> <ref>PMID:10811883</ref> <ref>PMID:11226248</ref> <ref>PMID:15341515</ref> <ref>PMID:16305624</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 22:

	==See Also==		==See Also==
-	*[[Gamma secretase ~~complex~~\|Gamma secretase ~~complex~~]]	+	*[[Gamma secretase\|Gamma secretase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</SX>		</SX>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bai~~, X C~~]]	+	[[Category: Bai XC]]
-	[[Category: Rajendra, E]]	+	[[Category: Rajendra E]]
-	[[Category: Scheres~~, S H.W~~]]	+	[[Category: Scheres SHW]]
-	[[Category: Shi~~, Y G~~]]	+	[[Category: Shi YG]]
-	[[Category: Yang~~, G H]]~~	+	[[Category: Yang GH]]
-	~~[[Category: Hydrolase~~]]	+

OCA at 19:54, 10 April 2020

2020-04-10T19:54:03Z

←Older revision		Revision as of 19:54, 10 April 2020
Line 3:		Line 3:
	<SX load='5fn3' size='340' side='right' viewer='molstar' caption='[[5fn3]], [[Resolution\|resolution]] 4.10Å' scene=''>		<SX load='5fn3' size='340' side='right' viewer='molstar' caption='[[5fn3]], [[Resolution\|resolution]] 4.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5fn3]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FN3 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5FN3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5fn3]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FN3 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5FN3 FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5fn2\|5fn2]], [[5fn4\|5fn4]], [[5fn5\|5fn5]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5fn2\|5fn2]], [[5fn4\|5fn4]], [[5fn5\|5fn5]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NCSTN, KIAA0253, UNQ1874/PRO4317 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PSEN1, AD3, PS1, PSNL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), APH1A, PSF, CGI-78, UNQ579/PRO1141 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PSENEN, PEN2, MDS033 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NCSTN, KIAA0253, UNQ1874/PRO4317 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PSEN1, AD3, PS1, PSNL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), APH1A, PSF, CGI-78, UNQ579/PRO1141 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PSENEN, PEN2, MDS033 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5fn3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fn3 OCA], [http://pdbe.org/5fn3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fn3 RCSB], [http://www.ebi.ac.uk/pdbsum/5fn3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fn3 ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5fn3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fn3 OCA], [http://pdbe.org/5fn3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fn3 RCSB], [http://www.ebi.ac.uk/pdbsum/5fn3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fn3 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==

OCA at 18:17, 6 March 2020

2020-03-06T18:17:38Z

←Older revision		Revision as of 18:17, 6 March 2020
Line 1:		Line 1:

	==Cryo-EM structure of gamma secretase in class 1 of the apo- state ensemble==		==Cryo-EM structure of gamma secretase in class 1 of the apo- state ensemble==
-	<~~StructureSection~~ load='5fn3' size='340' side='right' caption='[[5fn3]], [[Resolution\|resolution]] 4.10Å' scene=''>	+	<SX load='5fn3' size='340' side='right' viewer='molstar' caption='[[5fn3]], [[Resolution\|resolution]] 4.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5fn3]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FN3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FN3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5fn3]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FN3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FN3 FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5fn2\|5fn2]], [[5fn4\|5fn4]], [[5fn5\|5fn5]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5fn2\|5fn2]], [[5fn4\|5fn4]], [[5fn5\|5fn5]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NCSTN, KIAA0253, UNQ1874/PRO4317 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PSEN1, AD3, PS1, PSNL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), APH1A, PSF, CGI-78, UNQ579/PRO1141 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PSENEN, PEN2, MDS033 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5fn3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fn3 OCA], [http://pdbe.org/5fn3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fn3 RCSB], [http://www.ebi.ac.uk/pdbsum/5fn3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fn3 ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5fn3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fn3 OCA], [http://pdbe.org/5fn3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fn3 RCSB], [http://www.ebi.ac.uk/pdbsum/5fn3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fn3 ProSAT]</span></td></tr>
	</table>		</table>
Line 20:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 5fn3" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5fn3" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Gamma secretase complex\|Gamma secretase complex]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
-	</~~StructureSection~~>	+	</SX>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Bai, X C]]		[[Category: Bai, X C]]
	[[Category: Rajendra, E]]		[[Category: Rajendra, E]]

OCA at 15:01, 22 December 2016

2016-12-22T15:01:38Z

←Older revision		Revision as of 15:01, 22 December 2016
Line 1:		Line 1:
		+
	==Cryo-EM structure of gamma secretase in class 1 of the apo- state ensemble==		==Cryo-EM structure of gamma secretase in class 1 of the apo- state ensemble==
	<StructureSection load='5fn3' size='340' side='right' caption='[[5fn3]], [[Resolution\|resolution]] 4.10Å' scene=''>		<StructureSection load='5fn3' size='340' side='right' caption='[[5fn3]], [[Resolution\|resolution]] 4.10Å' scene=''>
Line 4:		Line 5:
	<table><tr><td colspan='2'>[[5fn3]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FN3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FN3 FirstGlance]. <br>		<table><tr><td colspan='2'>[[5fn3]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FN3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FN3 FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5fn2\|5fn2]], [[5fn4\|5fn4]], [[5fn5\|5fn5]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5fn2\|5fn2]], [[5fn4\|5fn4]], [[5fn5\|5fn5]]</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5fn3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fn3 OCA], [http://pdbe.org/5fn3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fn3 RCSB], [http://www.ebi.ac.uk/pdbsum/5fn3 PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5fn3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fn3 OCA], [http://pdbe.org/5fn3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fn3 RCSB], [http://www.ebi.ac.uk/pdbsum/5fn3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fn3 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==

OCA at 13:52, 16 December 2015

2015-12-16T13:52:31Z

←Older revision		Revision as of 13:52, 16 December 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Cryo-EM structure of gamma secretase in class 1 of the apo- state ensemble==
		+	<StructureSection load='5fn3' size='340' side='right' caption='[[5fn3]], [[Resolution\|resolution]] 4.10Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5fn3]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FN3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FN3 FirstGlance]. <br>
		+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5fn2\|5fn2]], [[5fn4\|5fn4]], [[5fn5\|5fn5]]</td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5fn3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fn3 OCA], [http://pdbe.org/5fn3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fn3 RCSB], [http://www.ebi.ac.uk/pdbsum/5fn3 PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/PEN2_HUMAN PEN2_HUMAN]] Hidradenitis suppurativa. The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/NICA_HUMAN NICA_HUMAN]] Hidradenitis suppurativa. The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/PSN1_HUMAN PSN1_HUMAN]] Defects in PSEN1 are a cause of Alzheimer disease type 3 (AD3) [MIM:[http://omim.org/entry/607822 607822]]. AD3 is a familial early-onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death.<ref>PMID:12058025</ref> <ref>PMID:7596406</ref> <ref>PMID:8634711</ref> <ref>PMID:8634712</ref> <ref>PMID:7651536</ref> <ref>PMID:7550356</ref> <ref>PMID:8733303</ref> <ref>PMID:9225696</ref> <ref>PMID:9298817</ref> <ref>PMID:9172170</ref> <ref>PMID:9833068</ref> <ref>PMID:9384602</ref> <ref>PMID:9521423</ref> <ref>PMID:10200054</ref> <ref>PMID:9719376</ref> <ref>PMID:9507958</ref> <ref>PMID:9831473</ref> <ref>PMID:10441572</ref> <ref>PMID:10090481</ref> <ref>PMID:10447269</ref> <ref>PMID:10533070</ref> <ref>PMID:10025789</ref> <ref>PMID:10208579</ref> <ref>PMID:10439444</ref> <ref>PMID:10631141</ref> <ref>PMID:10644793</ref> <ref>PMID:11027672</ref> [:]<ref>PMID:11710891</ref> <ref>PMID:11920851</ref> <ref>PMID:12048239</ref> <ref>PMID:12484344</ref> <ref>PMID:12493737</ref> Defects in PSEN1 are a cause of frontotemporal dementia (FTD) [MIM:[http://omim.org/entry/600274 600274]]. Defects in PSEN1 are the cause of cardiomyopathy dilated type 1U (CMD1U) [MIM:[http://omim.org/entry/613694 613694]]. It is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.<ref>PMID:17186461</ref> Defects in PSEN1 are the cause of familial acne inversa type 3 (ACNINV3) [MIM:[http://omim.org/entry/613737 613737]]. A chronic relapsing inflammatory disease of the hair follicles characterized by recurrent draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty.<ref>PMID:20929727</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PEN2_HUMAN PEN2_HUMAN]] Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (beta-amyloid precursor protein). Probably represents the last step of maturation of gamma-secretase, facilitating endoproteolysis of presenilin and conferring gamma-secretase activity.<ref>PMID:12522139</ref> <ref>PMID:12763021</ref> [[http://www.uniprot.org/uniprot/NICA_HUMAN NICA_HUMAN]] Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (beta-amyloid precursor protein). It probably represents a stabilizing cofactor required for the assembly of the gamma-secretase complex. [[http://www.uniprot.org/uniprot/APH1A_HUMAN APH1A_HUMAN]] Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors and APP (beta-amyloid precursor protein). It probably represents a stabilizing cofactor for the presenilin homodimer that promotes the formation of a stable complex.<ref>PMID:12297508</ref> <ref>PMID:12522139</ref> <ref>PMID:12763021</ref> [[http://www.uniprot.org/uniprot/PSN1_HUMAN PSN1_HUMAN]] Probable catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (beta-amyloid precursor protein). Requires the other members of the gamma-secretase complex to have a protease activity. May play a role in intracellular signaling and gene expression or in linking chromatin to the nuclear membrane. Stimulates cell-cell adhesion though its association with the E-cadherin/catenin complex. Under conditions of apoptosis or calcium influx, cleaves E-cadherin promoting the disassembly of the E-cadherin/catenin complex and increasing the pool of cytoplasmic beta-catenin, thus negatively regulating Wnt signaling. May also play a role in hematopoiesis.<ref>PMID:10545183</ref> <ref>PMID:10593990</ref> <ref>PMID:10206644</ref> <ref>PMID:10899933</ref> <ref>PMID:10811883</ref> <ref>PMID:11226248</ref> <ref>PMID:15341515</ref> <ref>PMID:16305624</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Human gamma-Secretase is an intra-membrane protease that cleaves many substrates. Aberrant cleavage of Notch is implicated in cancer, while abnormalities in cutting amyloid precursor protein lead to Alzheimer's disease. Our previous cryo-EM structure of gamma-secretase revealed considerable disorder in its catalytic subunit presenilin. Here, we describe an image classification procedure that characterizes molecular plasticity at the secondary structure level, and apply this method to identify three distinct conformations in our previous sample. In one of these conformations, an additional transmembrane helix is visible that cannot be attributed to known components of gamma-secretase. In addition, we present a gamma-secretase structure in complex with the dipeptidic inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT). Our results reveal how conformational mobility in the second and sixth transmembrane helices of presenilin is greatly reduced upon binding of DAPT or the additional helix, and form the basis for a new model of how substrate enters the transmembrane domain.

-	~~The entry 5fn3 is ON HOLD until Paper Publication~~	+	Sampling the conformational space of the catalytic subunit of human gamma-secretase.,Bai XC, Rajendra E, Yang G, Shi Y, Scheres SH Elife. 2015 Dec 1;4. pii: e11182. doi: 10.7554/eLife.11182. PMID:26623517<ref>PMID:26623517</ref>

-	~~Authors: Bai~~, X.~~C., Rajendra, E., Yang, G.H., Shi, Y.G., Scheres,~~ S.~~H.W~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description: Cryo-EM structure of gamma secretase in~~ class ~~1 of the apo~~-~~state ensemble~~	+	<div class="pdbe-citations 5fn3" style="background-color:#fffaf0;"></div>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	== References ==
-	[[Category: ~~Yang~~, ~~G.H~~]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Bai, X C]]
	[[Category: Rajendra, E]]		[[Category: Rajendra, E]]
-	[[Category: ~~Bai~~, X.C]]	+	[[Category: Scheres, S H.W]]
-	[[Category: Shi, Y.G]]	+	[[Category: Shi, Y G]]
-	[[Category: ~~Scheres~~, S.H.W]]	+	[[Category: Yang, G H]]
		+	[[Category: Hydrolase]]

OCA: Protected "5fn3" [edit=sysop:move=sysop]

2015-12-01T03:40:13Z

Protected "5fn3" [edit=sysop:move=sysop]

←Older revision

Revision as of 03:40, 1 December 2015

OCA: New page: '''Unreleased structure''' The entry 5fn3 is ON HOLD until Paper Publication Authors: Bai, X.C., Rajendra, E., Yang, G.H., Shi, Y.G., Scheres, S.H.W. Description: Cryo-EM structure of ...

2015-12-01T03:40:12Z

New page: '''Unreleased structure''' The entry 5fn3 is ON HOLD until Paper Publication Authors: Bai, X.C., Rajendra, E., Yang, G.H., Shi, Y.G., Scheres, S.H.W. Description: Cryo-EM structure of ...

New page

'''Unreleased structure'''

The entry 5fn3 is ON HOLD until Paper Publication

Authors: Bai, X.C., Rajendra, E., Yang, G.H., Shi, Y.G., Scheres, S.H.W.

Description: Cryo-EM structure of gamma secretase in class 1 of the apo-state ensemble
[[Category: Unreleased Structures]]
[[Category: Yang, G.H]]
[[Category: Rajendra, E]]
[[Category: Bai, X.C]]
[[Category: Shi, Y.G]]
[[Category: Scheres, S.H.W]]