3ovl - Revision history

OCA at 10:36, 21 February 2024

OCA — Wed, 21 Feb 2024 10:36:49 GMT

←Older revision		Revision as of 10:36, 21 February 2024
Line 3:		Line 3:
	<StructureSection load='3ovl' size='340' side='right'caption='[[3ovl]], [[Resolution\|resolution]] 1.81Å' scene=''>		<StructureSection load='3ovl' size='340' side='right'caption='[[3ovl]], [[Resolution\|resolution]] 1.81Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3ovl]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OVL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OVL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3ovl]] is a 1 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=3OVL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OVL FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=ORA:7-HYDROXY-8-[(E)-PHENYLDIAZENYL]NAPHTHALENE-1,3-DISULFONIC+ACID'>ORA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.81Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2on9\|2on9]], [[3fqp\|3fqp]]</div~~></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=ORA:7-HYDROXY-8-[(E)-PHENYLDIAZENYL]NAPHTHALENE-1,3-DISULFONIC+ACID'>ORA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=3ovl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ovl OCA], [https://pdbe.org/3ovl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ovl RCSB], [https://www.ebi.ac.uk/pdbsum/3ovl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ovl 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=3ovl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ovl OCA], [https://pdbe.org/3ovl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ovl RCSB], [https://www.ebi.ac.uk/pdbsum/3ovl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ovl ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://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:[https://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:[https://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:[https://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:[https://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>	+	[https://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:[https://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:[https://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:[https://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:[https://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 ==
-	[[https://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/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 ==~~	+
-	Diagnosing and treating Alzheimer's and other diseases associated with amyloid fibers remains a great challenge despite intensive research. To aid in this effort, we present atomic structures of fiber-forming segments of proteins involved in Alzheimer's disease in complex with small molecule binders, determined by X-ray microcrystallography. The fiber-like complexes consist of pairs of beta-sheets, with small molecules binding between the sheets, roughly parallel to the fiber axis. The structures suggest that apolar molecules drift along the fiber, consistent with the observation of nonspecific binding to a variety of amyloid proteins. In contrast, negatively charged orange-G binds specifically to lysine side chains of adjacent sheets. These structures provide molecular frameworks for the design of diagnostics and drugs for protein aggregation diseases.	+
-		+
-	Towards a pharmacophore for amyloid.,Landau M, Sawaya MR, Faull KF, Laganowsky A, Jiang L, Sievers SA, Liu J, Barrio JR, Eisenberg D PLoS Biol. 2011 Jun;9(6):e1001080. Epub 2011 Jun 14. PMID:21695112<ref>PMID:21695112</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3ovl" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
Line 29:		Line 20:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Eisenberg, D]]	+	[[Category: Eisenberg D]]
-	[[Category: Landau, M]]	+	[[Category: Landau M]]
-	~~[[Category: Amyloid-like protofibril in complex with a small-molecule binder]]~~	+
-	~~[[Category: Protein fibril~~]]	+

OCA at 10:59, 18 May 2022

OCA — Wed, 18 May 2022 10:59:02 GMT

←Older revision		Revision as of 10:59, 18 May 2022
Line 1:		Line 1:

	==Structure of an amyloid forming peptide VQIVYK from the TAU protein in complex with orange G==		==Structure of an amyloid forming peptide VQIVYK from the TAU protein in complex with orange G==
-	<StructureSection load='3ovl' size='340' side='right' caption='[[3ovl]], [[Resolution\|resolution]] 1.81Å' scene=''>	+	<StructureSection load='3ovl' size='340' side='right'caption='[[3ovl]], [[Resolution\|resolution]] 1.81Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3ovl]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OVL OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3OVL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3ovl]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OVL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OVL FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=ORA:7-HYDROXY-8-[(E)-PHENYLDIAZENYL]NAPHTHALENE-1,3-DISULFONIC+ACID'>ORA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=ORA:7-HYDROXY-8-[(E)-PHENYLDIAZENYL]NAPHTHALENE-1,3-DISULFONIC+ACID'>ORA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2on9\|2on9]], [[3fqp\|3fqp]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2on9\|2on9]], [[3fqp\|3fqp]]</div></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=3ovl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ovl OCA], [~~http~~://pdbe.org/3ovl PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3ovl RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3ovl PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3ovl 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=3ovl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ovl OCA], [https://pdbe.org/3ovl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ovl RCSB], [https://www.ebi.ac.uk/pdbsum/3ovl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ovl ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== 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>	+	[[https://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:[https://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:[https://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:[https://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:[https://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/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/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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 23:

	==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]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Eisenberg, D]]		[[Category: Eisenberg, D]]
	[[Category: Landau, M]]		[[Category: Landau, M]]
	[[Category: Amyloid-like protofibril in complex with a small-molecule binder]]		[[Category: Amyloid-like protofibril in complex with a small-molecule binder]]
	[[Category: Protein fibril]]		[[Category: Protein fibril]]

OCA at 15:22, 4 August 2016

OCA — Thu, 04 Aug 2016 15:22:45 GMT

←Older revision		Revision as of 15:22, 4 August 2016
Line 1:		Line 1:
		+
	==Structure of an amyloid forming peptide VQIVYK from the TAU protein in complex with orange G==		==Structure of an amyloid forming peptide VQIVYK from the TAU protein in complex with orange G==
	<StructureSection load='3ovl' size='340' side='right' caption='[[3ovl]], [[Resolution\|resolution]] 1.81Å' scene=''>		<StructureSection load='3ovl' size='340' side='right' caption='[[3ovl]], [[Resolution\|resolution]] 1.81Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=ORA:7-HYDROXY-8-[(E)-PHENYLDIAZENYL]NAPHTHALENE-1,3-DISULFONIC+ACID'>ORA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=ORA:7-HYDROXY-8-[(E)-PHENYLDIAZENYL]NAPHTHALENE-1,3-DISULFONIC+ACID'>ORA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2on9\|2on9]], [[3fqp\|3fqp]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2on9\|2on9]], [[3fqp\|3fqp]]</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=3ovl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ovl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ovl RCSB], [http://www.ebi.ac.uk/pdbsum/3ovl 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=3ovl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ovl OCA], [http://pdbe.org/3ovl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ovl RCSB], [http://www.ebi.ac.uk/pdbsum/3ovl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ovl ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 20:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3ovl" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Microtubule-associated protein\|Microtubule-associated protein]]
		+	*[[Tau protein\|Tau protein]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:16, 19 December 2014

OCA — Fri, 19 Dec 2014 07:16:02 GMT

←Older revision		Revision as of 07:16, 19 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3ovl\| PDB=3ovl \| SCENE= }}~~	+	==Structure of an amyloid forming peptide VQIVYK from the TAU protein in complex with orange G==
-	===Structure of an amyloid forming peptide VQIVYK from the TAU protein in complex with orange G===	+	<StructureSection load='3ovl' size='340' side='right' caption='[[3ovl]], [[Resolution\|resolution]] 1.81Å' scene=''>
-	~~{{ABSTRACT_PUBMED_21695112}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3ovl]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OVL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OVL FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=ORA:7-HYDROXY-8-[(E)-PHENYLDIAZENYL]NAPHTHALENE-1,3-DISULFONIC+ACID'>ORA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2on9\|2on9]], [[3fqp\|3fqp]]</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=3ovl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ovl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ovl RCSB], [http://www.ebi.ac.uk/pdbsum/3ovl 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/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 ==
		+	Diagnosing and treating Alzheimer's and other diseases associated with amyloid fibers remains a great challenge despite intensive research. To aid in this effort, we present atomic structures of fiber-forming segments of proteins involved in Alzheimer's disease in complex with small molecule binders, determined by X-ray microcrystallography. The fiber-like complexes consist of pairs of beta-sheets, with small molecules binding between the sheets, roughly parallel to the fiber axis. The structures suggest that apolar molecules drift along the fiber, consistent with the observation of nonspecific binding to a variety of amyloid proteins. In contrast, negatively charged orange-G binds specifically to lysine side chains of adjacent sheets. These structures provide molecular frameworks for the design of diagnostics and drugs for protein aggregation diseases.

-	~~==Disease==~~	+	Towards a pharmacophore for amyloid.,Landau M, Sawaya MR, Faull KF, Laganowsky A, Jiang L, Sievers SA, Liu J, Barrio JR, Eisenberg D PLoS Biol. 2011 Jun;9(6):e1001080. Epub 2011 Jun 14. PMID:21695112<ref>PMID:21695112</ref>
-	[[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==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[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>
-		+	== References ==
-	==~~About this Structure==~~	+	<references/>
-	~~[[3ovl]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OVL OCA].~~	+	__TOC__
-		+	</StructureSection>
-	~~==Reference~~==	+	[[Category: Eisenberg, D]]
-	~~<ref group="xtra">PMID:021695112</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	[[Category: Landau, M]]
-	[[Category: Eisenberg, D.]]	+
-	[[Category: Landau, M.]]	+
	[[Category: Amyloid-like protofibril in complex with a small-molecule binder]]		[[Category: Amyloid-like protofibril in complex with a small-molecule binder]]
	[[Category: Protein fibril]]		[[Category: Protein fibril]]

OCA at 21:21, 24 March 2013

OCA — Sun, 24 Mar 2013 21:21:05 GMT

←Older revision		Revision as of 21:21, 24 March 2013
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-	[[Image:3ovl.jpg\|left\|200px]]
-
-	<!--
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	{{STRUCTURE_3ovl\| PDB=3ovl \| SCENE= }}		{{STRUCTURE_3ovl\| PDB=3ovl \| SCENE= }}
-
	===Structure of an amyloid forming peptide VQIVYK from the TAU protein in complex with orange G===		===Structure of an amyloid forming peptide VQIVYK from the TAU protein in complex with orange G===
		+	{{ABSTRACT_PUBMED_21695112}}

		+	==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==
-	~~The line below this paragraph, {{ABSTRACT_PUBMED_21695112}}, adds the Publication Abstract to the page~~	+	[[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>
-	~~(as it appears on PubMed at~~ http://www.~~pubmed~~.~~gov)~~, ~~where 21695112 is~~ the ~~PubMed ID number~~.	+
-	-->	+
-	~~{{ABSTRACT_PUBMED_21695112}}~~	+

	==About this Structure==		==About this Structure==
Line 22:		Line 13:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:021695112</ref><references group="xtra"/>	+	<ref group="xtra">PMID:021695112</ref><references group="xtra"/><references/>
	[[Category: Eisenberg, D.]]		[[Category: Eisenberg, D.]]
	[[Category: Landau, M.]]		[[Category: Landau, M.]]
	[[Category: Amyloid-like protofibril in complex with a small-molecule binder]]		[[Category: Amyloid-like protofibril in complex with a small-molecule binder]]
	[[Category: Protein fibril]]		[[Category: Protein fibril]]

OCA at 18:45, 6 July 2011

OCA — Wed, 06 Jul 2011 18:45:39 GMT

←Older revision		Revision as of 18:45, 6 July 2011
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3ovl.jpg\|left\|200px]]

-	The ~~entry 3ovl~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3ovl", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3ovl\| PDB=3ovl \| SCENE= }}

-	~~Authors: Landau, M., Eisenberg, D.~~	+	===Structure of an amyloid forming peptide VQIVYK from the TAU protein in complex with orange G===

-	~~Description~~: Structure ~~of an amyloid forming peptide VQIVYK~~ from ~~the TAU protein~~ in complex with ~~orange G~~	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_21695112}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 21695112 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_21695112}}
		+
		+	==About this Structure==
		+	[[3ovl]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OVL OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:021695112</ref><references group="xtra"/>
		+	[[Category: Eisenberg, D.]]
		+	[[Category: Landau, M.]]
		+	[[Category: Amyloid-like protofibril in complex with a small-molecule binder]]
		+	[[Category: Protein fibril]]

OCA: Protected "3ovl" [edit=sysop:move=sysop]

OCA — Wed, 29 Dec 2010 18:12:26 GMT

Protected "3ovl" [edit=sysop:move=sysop]

←Older revision

Revision as of 18:12, 29 December 2010

OCA at 18:12, 29 December 2010

OCA — Wed, 29 Dec 2010 18:12:25 GMT

←Older revision		Revision as of 18:12, 29 December 2010
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3ovl is ON HOLD	+	The entry 3ovl is ON HOLD until Paper Publication

	Authors: Landau, M., Eisenberg, D.		Authors: Landau, M., Eisenberg, D.

	Description: Structure of an amyloid forming peptide VQIVYK from the TAU protein in complex with orange G		Description: Structure of an amyloid forming peptide VQIVYK from the TAU protein in complex with orange G
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Nov 3 10:03:54 2010''

OCA at 06:53, 3 November 2010

OCA — Wed, 03 Nov 2010 06:53:15 GMT

←Older revision		Revision as of 06:53, 3 November 2010
Line 5:		Line 5:
	Authors: Landau, M., Eisenberg, D.		Authors: Landau, M., Eisenberg, D.

-	Description: ~~STRUCTURE OF AN AMYLOID FORMING PEPTIDE~~ VQIVYK ~~FROM THE~~ TAU ~~PROTEIN IN COMPLEX WITH ORANGE~~ G	+	Description: Structure of an amyloid forming peptide VQIVYK from the TAU protein in complex with orange G

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Sep 29 07~~:57:33 2010''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Nov 3 10:03:54 2010''

OCA at 04:48, 29 September 2010

OCA — Wed, 29 Sep 2010 04:48:18 GMT

←Older revision		Revision as of 04:48, 29 September 2010
Line 3:		Line 3:
	The entry 3ovl is ON HOLD		The entry 3ovl is ON HOLD

-	Authors: Landau, M~~., Sawaya, M.R., Faull, K.F., Sievers, S., Laganowsky, A., Liu, J., Barrio, J~~., Eisenberg, D.	+	Authors: Landau, M., Eisenberg, D.

	Description: STRUCTURE OF AN AMYLOID FORMING PEPTIDE VQIVYK FROM THE TAU PROTEIN IN COMPLEX WITH ORANGE G		Description: STRUCTURE OF AN AMYLOID FORMING PEPTIDE VQIVYK FROM THE TAU PROTEIN IN COMPLEX WITH ORANGE G

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Sep ~~22 14~~:35:34 2010''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Sep 29 07:57:33 2010''