4y5i - Revision history

OCA at 10:53, 10 January 2024

OCA — Wed, 10 Jan 2024 10:53:03 GMT

←Older revision		Revision as of 10:53, 10 January 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4y5i]] 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=4Y5I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y5I FirstGlance]. <br>		<table><tr><td colspan='2'>[[4y5i]] 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=4Y5I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y5I FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PIP:PIPERIDINE'>PIP</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></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]] 1.4Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PIP:PIPERIDINE'>PIP</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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=4y5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y5i OCA], [https://pdbe.org/4y5i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y5i RCSB], [https://www.ebi.ac.uk/pdbsum/4y5i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y5i ProSAT]</span></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=4y5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y5i OCA], [https://pdbe.org/4y5i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y5i RCSB], [https://www.ebi.ac.uk/pdbsum/4y5i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y5i ProSAT]</span></td></tr>
	</table>		</table>

OCA at 07:59, 3 May 2023

OCA — Wed, 03 May 2023 07:59:27 GMT

←Older revision		Revision as of 07:59, 3 May 2023
Line 3:		Line 3:
	<StructureSection load='4y5i' size='340' side='right'caption='[[4y5i]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='4y5i' size='340' side='right'caption='[[4y5i]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4y5i]] is a 4 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=4Y5I OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4Y5I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4y5i]] 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=4Y5I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y5I FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:~~CHLORIDE~~+~~ION~~'>CL</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PIP:PIPERIDINE'>PIP</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
-	~~<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=~~ACE~~:~~ACETYL~~+~~GROUP~~'>~~ACE~~</scene>, <scene name='pdbligand=PIP:PIPERIDINE'>PIP</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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=4y5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y5i OCA], [https://pdbe.org/4y5i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y5i RCSB], [https://www.ebi.ac.uk/pdbsum/4y5i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y5i ProSAT]</span></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4y3b\|4y3b]], [[4y32\|4y32]], [[4y3v\|4y3v]]</td></tr>~~	+
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SFN, HME1 ([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=4y5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y5i OCA], [~~http~~://pdbe.org/4y5i PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4y5i RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4y5i PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4y5i ProSAT]</span></td></tr>	+
	</table>		</table>
-	== Disease ==
-	[[http://www.uniprot.org/uniprot/TAU_HUMAN TAU_HUMAN]] Note=In Alzheimer disease, the neuronal cytoskeleton in the brain is progressively disrupted and replaced by tangles of paired helical filaments (PHF) and straight filaments, mainly composed of hyperphosphorylated forms of TAU (PHF-TAU or AD P-TAU). O-GlcNAcylation is greatly reduced in Alzheimer disease brain cerebral cortex leading to an increase in TAU/MAPT phosphorylations.<ref>PMID:19451179</ref> <ref>PMID:2484340</ref> <ref>PMID:14517953</ref> Defects in MAPT are a cause of frontotemporal dementia (FTD) [MIM:[http://omim.org/entry/600274 600274]]; also called frontotemporal dementia (FTD), pallido-ponto-nigral degeneration (PPND) or historically termed Pick complex. This form of frontotemporal dementia is characterized by presenile dementia with behavioral changes, deterioration of cognitive capacities and loss of memory. In some cases, parkinsonian symptoms are prominent. Neuropathological changes include frontotemporal atrophy often associated with atrophy of the basal ganglia, substantia nigra, amygdala. In most cases, protein tau deposits are found in glial cells and/or neurons.<ref>PMID:19451179</ref> <ref>PMID:2484340</ref> <ref>PMID:14517953</ref> <ref>PMID:9629852</ref> <ref>PMID:9736786</ref> <ref>PMID:9641683</ref> <ref>PMID:9789048</ref> <ref>PMID:9973279</ref> <ref>PMID:10553987</ref> <ref>PMID:10214944</ref> <ref>PMID:10374757</ref> <ref>PMID:10489057</ref> <ref>PMID:10208578</ref> <ref>PMID:11117541</ref> <ref>PMID:10802785</ref> <ref>PMID:11071507</ref> <ref>PMID:11585254</ref> <ref>PMID:11278002</ref> <ref>PMID:12473774</ref> <ref>PMID:11921059</ref> <ref>PMID:11906000</ref> <ref>PMID:11889249</ref> <ref>PMID:12509859</ref> <ref>PMID:16240366</ref> <ref>PMID:15883319</ref> Defects in MAPT are a cause of Pick disease of the brain (PIDB) [MIM:[http://omim.org/entry/172700 172700]]. It is a rare form of dementia pathologically defined by severe atrophy, neuronal loss and gliosis. It is characterized by the occurrence of tau-positive inclusions, swollen neurons (Pick cells) and argentophilic neuronal inclusions known as Pick bodies that disproportionally affect the frontal and temporal cortical regions. Clinical features include aphasia, apraxia, confusion, anomia, memory loss and personality deterioration.<ref>PMID:19451179</ref> <ref>PMID:2484340</ref> <ref>PMID:14517953</ref> <ref>PMID:10604746</ref> <ref>PMID:11117542</ref> <ref>PMID:11089577</ref> <ref>PMID:11601501</ref> <ref>PMID:11891833</ref> Note=Defects in MAPT are a cause of corticobasal degeneration (CBD). It is marked by extrapyramidal signs and apraxia and can be associated with memory loss. Neuropathologic features may overlap Alzheimer disease, progressive supranuclear palsy, and Parkinson disease.<ref>PMID:19451179</ref> <ref>PMID:2484340</ref> <ref>PMID:14517953</ref> Defects in MAPT are a cause of progressive supranuclear palsy type 1 (PSNP1) [MIM:[http://omim.org/entry/601104 601104]]; also abbreviated as PSP and also known as Steele-Richardson-Olszewski syndrome. PSNP1 is characterized by akinetic-rigid syndrome, supranuclear gaze palsy, pyramidal tract dysfunction, pseudobulbar signs and cognitive capacities deterioration. Neurofibrillary tangles and gliosis but no amyloid plaques are found in diseased brains. Most cases appear to be sporadic, with a significant association with a common haplotype including the MAPT gene and the flanking regions. Familial cases show an autosomal dominant pattern of transmission with incomplete penetrance; genetic analysis of a few cases showed the occurrence of tau mutations, including a deletion of Asn-613.<ref>PMID:19451179</ref> <ref>PMID:2484340</ref> <ref>PMID:14517953</ref> <ref>PMID:10534245</ref> <ref>PMID:11220749</ref> <ref>PMID:12325083</ref> <ref>PMID:14991829</ref> <ref>PMID:14991828</ref> <ref>PMID:16157753</ref> Defects in MAPT are a cause of Parkinson-dementia syndrome (PARDE) [MIM:[http://omim.org/entry/260540 260540]]. A syndrome characterized by parkinsonism tremor, rigidity, dementia, ophthalmoparesis and pyramidal signs. Neurofibrillary degeneration occurs in the hippocampus, basal ganglia and brainstem nuclei.<ref>PMID:19451179</ref> <ref>PMID:2484340</ref> <ref>PMID:14517953</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/1433S_HUMAN 1433S_HUMAN]] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression. [[http://www.uniprot.org/uniprot/TAU_HUMAN TAU_HUMAN]] Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity. The C-terminus binds axonal microtubules while the N-terminus binds neural plasma membrane components, suggesting that tau functions as a linker protein between both. Axonal polarity is predetermined by TAU/MAPT localization (in the neuronal cell) in the domain of the cell body defined by the centrosome. The short isoforms allow plasticity of the cytoskeleton whereas the longer isoforms may preferentially play a role in its stabilization.<ref>PMID:21985311</ref>	+	[https://www.uniprot.org/uniprot/1433S_HUMAN 1433S_HUMAN] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 20:

	==See Also==		==See Also==
-	*[[Microtubule-associated protein\|Microtubule-associated protein]]	+	*[[Microtubule-associated protein 3D structures\|Microtubule-associated protein 3D structures]]
-	*[[Tau protein\|Tau protein]]	+	*[[Tau protein 3D structures\|Tau protein 3D structures]]
	*[[14-3-3 protein 3D structures\|14-3-3 protein 3D structures]]		*[[14-3-3 protein 3D structures\|14-3-3 protein 3D structures]]
	== References ==		== References ==
Line 32:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bartel, M]]	+	[[Category: Bartel M]]
-	[[Category: Brunsveld, L]]	+	[[Category: Brunsveld L]]
-	[[Category: Leysen, S]]	+	[[Category: Leysen S]]
-	[[Category: Milroy, L]]	+	[[Category: Milroy L]]
-	[[Category: Ottmann, C]]	+	[[Category: Ottmann C]]
-	~~[[Category: 14-3-3 sigma]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Peptide-hybrid]]~~	+
-	~~[[Category: Protein-protein interaction]]~~	+
-	~~[[Category: Signaling protein]]~~	+
-	~~[[Category: Tau~~]]	+

OCA at 12:30, 13 March 2019

OCA — Wed, 13 Mar 2019 12:30:16 GMT

←Older revision		Revision as of 12:30, 13 March 2019
Line 1:		Line 1:
		+
	==Crystal structure of C-terminal modified Tau peptide-hybrid 126B with 14-3-3sigma==		==Crystal structure of C-terminal modified Tau peptide-hybrid 126B with 14-3-3sigma==
-	<StructureSection load='4y5i' size='340' side='right' caption='[[4y5i]], [[Resolution\|resolution]] 1.40Å' scene=''>	+	<StructureSection load='4y5i' size='340' side='right'caption='[[4y5i]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4y5i]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Y5I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Y5I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4y5i]] is a 4 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=4Y5I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Y5I FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=PIP:PIPERIDINE'>PIP</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=PIP:PIPERIDINE'>PIP</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4y3b\|4y3b]], [[4y32\|4y32]], [[4y3v\|4y3v]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4y3b\|4y3b]], [[4y32\|4y32]], [[4y3v\|4y3v]]</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=4y5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y5i OCA], [http://pdbe.org/4y5i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4y5i RCSB], [http://www.ebi.ac.uk/pdbsum/4y5i PDBsum]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SFN, HME1 ([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=4y5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y5i OCA], [http://pdbe.org/4y5i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4y5i RCSB], [http://www.ebi.ac.uk/pdbsum/4y5i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4y5i ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 23:
	</div>		</div>
	<div class="pdbe-citations 4y5i" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4y5i" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Microtubule-associated protein\|Microtubule-associated protein]]
		+	*[[Tau protein\|Tau protein]]
		+	*[[14-3-3 protein 3D structures\|14-3-3 protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Bartel, M]]		[[Category: Bartel, M]]
	[[Category: Brunsveld, L]]		[[Category: Brunsveld, L]]

OCA at 20:04, 13 January 2016

OCA — Wed, 13 Jan 2016 20:04:06 GMT

←Older revision		Revision as of 20:04, 13 January 2016
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Crystal structure of C-terminal modified Tau peptide-hybrid 126B with 14-3-3sigma==
		+	<StructureSection load='4y5i' size='340' side='right' caption='[[4y5i]], [[Resolution\|resolution]] 1.40Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4y5i]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Y5I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Y5I FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=PIP:PIPERIDINE'>PIP</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4y3b\|4y3b]], [[4y32\|4y32]], [[4y3v\|4y3v]]</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=4y5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y5i OCA], [http://pdbe.org/4y5i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4y5i RCSB], [http://www.ebi.ac.uk/pdbsum/4y5i PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/TAU_HUMAN TAU_HUMAN]] Note=In Alzheimer disease, the neuronal cytoskeleton in the brain is progressively disrupted and replaced by tangles of paired helical filaments (PHF) and straight filaments, mainly composed of hyperphosphorylated forms of TAU (PHF-TAU or AD P-TAU). O-GlcNAcylation is greatly reduced in Alzheimer disease brain cerebral cortex leading to an increase in TAU/MAPT phosphorylations.<ref>PMID:19451179</ref> <ref>PMID:2484340</ref> <ref>PMID:14517953</ref> Defects in MAPT are a cause of frontotemporal dementia (FTD) [MIM:[http://omim.org/entry/600274 600274]]; also called frontotemporal dementia (FTD), pallido-ponto-nigral degeneration (PPND) or historically termed Pick complex. This form of frontotemporal dementia is characterized by presenile dementia with behavioral changes, deterioration of cognitive capacities and loss of memory. In some cases, parkinsonian symptoms are prominent. Neuropathological changes include frontotemporal atrophy often associated with atrophy of the basal ganglia, substantia nigra, amygdala. In most cases, protein tau deposits are found in glial cells and/or neurons.<ref>PMID:19451179</ref> <ref>PMID:2484340</ref> <ref>PMID:14517953</ref> <ref>PMID:9629852</ref> <ref>PMID:9736786</ref> <ref>PMID:9641683</ref> <ref>PMID:9789048</ref> <ref>PMID:9973279</ref> <ref>PMID:10553987</ref> <ref>PMID:10214944</ref> <ref>PMID:10374757</ref> <ref>PMID:10489057</ref> <ref>PMID:10208578</ref> <ref>PMID:11117541</ref> <ref>PMID:10802785</ref> <ref>PMID:11071507</ref> <ref>PMID:11585254</ref> <ref>PMID:11278002</ref> <ref>PMID:12473774</ref> <ref>PMID:11921059</ref> <ref>PMID:11906000</ref> <ref>PMID:11889249</ref> <ref>PMID:12509859</ref> <ref>PMID:16240366</ref> <ref>PMID:15883319</ref> Defects in MAPT are a cause of Pick disease of the brain (PIDB) [MIM:[http://omim.org/entry/172700 172700]]. It is a rare form of dementia pathologically defined by severe atrophy, neuronal loss and gliosis. It is characterized by the occurrence of tau-positive inclusions, swollen neurons (Pick cells) and argentophilic neuronal inclusions known as Pick bodies that disproportionally affect the frontal and temporal cortical regions. Clinical features include aphasia, apraxia, confusion, anomia, memory loss and personality deterioration.<ref>PMID:19451179</ref> <ref>PMID:2484340</ref> <ref>PMID:14517953</ref> <ref>PMID:10604746</ref> <ref>PMID:11117542</ref> <ref>PMID:11089577</ref> <ref>PMID:11601501</ref> <ref>PMID:11891833</ref> Note=Defects in MAPT are a cause of corticobasal degeneration (CBD). It is marked by extrapyramidal signs and apraxia and can be associated with memory loss. Neuropathologic features may overlap Alzheimer disease, progressive supranuclear palsy, and Parkinson disease.<ref>PMID:19451179</ref> <ref>PMID:2484340</ref> <ref>PMID:14517953</ref> Defects in MAPT are a cause of progressive supranuclear palsy type 1 (PSNP1) [MIM:[http://omim.org/entry/601104 601104]]; also abbreviated as PSP and also known as Steele-Richardson-Olszewski syndrome. PSNP1 is characterized by akinetic-rigid syndrome, supranuclear gaze palsy, pyramidal tract dysfunction, pseudobulbar signs and cognitive capacities deterioration. Neurofibrillary tangles and gliosis but no amyloid plaques are found in diseased brains. Most cases appear to be sporadic, with a significant association with a common haplotype including the MAPT gene and the flanking regions. Familial cases show an autosomal dominant pattern of transmission with incomplete penetrance; genetic analysis of a few cases showed the occurrence of tau mutations, including a deletion of Asn-613.<ref>PMID:19451179</ref> <ref>PMID:2484340</ref> <ref>PMID:14517953</ref> <ref>PMID:10534245</ref> <ref>PMID:11220749</ref> <ref>PMID:12325083</ref> <ref>PMID:14991829</ref> <ref>PMID:14991828</ref> <ref>PMID:16157753</ref> Defects in MAPT are a cause of Parkinson-dementia syndrome (PARDE) [MIM:[http://omim.org/entry/260540 260540]]. A syndrome characterized by parkinsonism tremor, rigidity, dementia, ophthalmoparesis and pyramidal signs. Neurofibrillary degeneration occurs in the hippocampus, basal ganglia and brainstem nuclei.<ref>PMID:19451179</ref> <ref>PMID:2484340</ref> <ref>PMID:14517953</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/1433S_HUMAN 1433S_HUMAN]] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression. [[http://www.uniprot.org/uniprot/TAU_HUMAN TAU_HUMAN]] Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity. The C-terminus binds axonal microtubules while the N-terminus binds neural plasma membrane components, suggesting that tau functions as a linker protein between both. Axonal polarity is predetermined by TAU/MAPT localization (in the neuronal cell) in the domain of the cell body defined by the centrosome. The short isoforms allow plasticity of the cytoskeleton whereas the longer isoforms may preferentially play a role in its stabilization.<ref>PMID:21985311</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The discovery of novel protein-protein interaction (PPI) modulators represents one of the great molecular challenges of the modern era. PPIs can be modulated by either inhibitor or stabilizer compounds, which target different though proximal regions of the protein interface. In principle, protein-stabilizer complexes can guide the design of PPI inhibitors (and vice versa). In the present work, we combine X-ray crystallographic data from both stabilizer and inhibitor co-crystal complexes of the adapter protein 14-3-3 to characterize, down to the atomic scale, inhibitors of the 14-3-3/Tau PPI, a potential drug target to treat Alzheimer's disease. The most potent compound notably inhibited the binding of phosphorylated full-length Tau to 14-3-3 according to NMR spectroscopy studies. Our work sets a precedent for the rational design of PPI inhibitors guided by PPI stabilizer-protein complexes while potentially enabling access to new synthetically tractable stabilizers of 14-3-3 and other PPIs.

-	~~The entry 4y5i is ON HOLD until Paper Publication~~	+	Stabilizer-Guided Inhibition of Protein-Protein Interactions.,Milroy LG, Bartel M, Henen MA, Leysen S, Adriaans JM, Brunsveld L, Landrieu I, Ottmann C Angew Chem Int Ed Engl. 2015 Nov 5. doi: 10.1002/anie.201507976. PMID:26537010<ref>PMID:26537010</ref>

-	~~Authors: Leysen~~, S.~~, Bartel, M., Milroy, L., Brunsveld, L., Ottmann, C~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description: Crystal structure of C~~-~~terminal modified Tau peptide~~-~~hybrid 126B with 14-3-3sigma~~	+	<div class="pdbe-citations 4y5i" style="background-color:#fffaf0;"></div>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	== References ==
-	~~[[Category: Ottmann, C]]~~	+	<references/>
-	[[Category: ~~Milroy~~, L]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Bartel, M]]
	[[Category: Brunsveld, L]]		[[Category: Brunsveld, L]]
	[[Category: Leysen, S]]		[[Category: Leysen, S]]
-	[[Category: ~~Bartel~~, M]]	+	[[Category: Milroy, L]]
		+	[[Category: Ottmann, C]]
		+	[[Category: 14-3-3 sigma]]
		+	[[Category: Inhibitor]]
		+	[[Category: Peptide-hybrid]]
		+	[[Category: Protein-protein interaction]]
		+	[[Category: Signaling protein]]
		+	[[Category: Tau]]

OCA at 10:06, 15 July 2015

OCA — Wed, 15 Jul 2015 10:06:40 GMT

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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4y5i is ON HOLD	+	The entry 4y5i is ON HOLD until Paper Publication

	Authors: Leysen, S., Bartel, M., Milroy, L., Brunsveld, L., Ottmann, C.		Authors: Leysen, S., Bartel, M., Milroy, L., Brunsveld, L., Ottmann, C.

OCA: Protected "4y5i" [edit=sysop:move=sysop]

OCA — Wed, 18 Feb 2015 12:03:07 GMT

Protected "4y5i" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:03, 18 February 2015

OCA: New page: '''Unreleased structure''' The entry 4y5i is ON HOLD Authors: Leysen, S., Bartel, M., Milroy, L., Brunsveld, L., Ottmann, C. Description: Crystal structure of C-terminal modified Tau p...

OCA — Wed, 18 Feb 2015 12:03:06 GMT

New page: '''Unreleased structure''' The entry 4y5i is ON HOLD Authors: Leysen, S., Bartel, M., Milroy, L., Brunsveld, L., Ottmann, C. Description: Crystal structure of C-terminal modified Tau p...

New page

'''Unreleased structure'''

The entry 4y5i is ON HOLD

Authors: Leysen, S., Bartel, M., Milroy, L., Brunsveld, L., Ottmann, C.

Description: Crystal structure of C-terminal modified Tau peptide-hybrid 126B with 14-3-3sigma
[[Category: Unreleased Structures]]
[[Category: Ottmann, C]]
[[Category: Milroy, L]]
[[Category: Brunsveld, L]]
[[Category: Leysen, S]]
[[Category: Bartel, M]]