OCA at 11:59, 8 November 2023

2023-11-08T11:59:38Z

←Older revision		Revision as of 11:59, 8 November 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 8g58 is ~~ON HOLD until Paper~~ Publication	+	==Tau (297-391) in vitro untwisted fibril==
		+	<StructureSection load='8g58' size='340' side='right'caption='[[8g58]]' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8g58]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8G58 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8G58 FirstGlance]. <br>
		+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Solid-state NMR</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=8g58 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8g58 OCA], [https://pdbe.org/8g58 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8g58 RCSB], [https://www.ebi.ac.uk/pdbsum/8g58 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8g58 ProSAT]</span></td></tr>
		+	</table>
		+	== 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>
		+	== 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The microtubule-associated protein tau aggregates into neurofibrillary tangles in Alzheimer's disease (AD). The main type of aggregates, the paired helical filaments (PHF), incorporate about 20% of the full-length protein into the rigid core. Recently, cryo-electron microscopy data showed that a protease-resistant fragment of tau (residues 297-391) self-assembles in vitro in the presence of divalent cations to form twisted filaments whose molecular structure resembles that of AD PHF tau [S. Lovestam et al., Elife 11, e76494 (2022)]. To investigate whether this tau construct is uniquely predisposed to this morphology and structure, we fibrillized tau (297-391) under the reported conditions and determined its structure using solid-state NMR spectroscopy. Unexpectedly, the protein assembled predominantly into nontwisting ribbons whose rigid core spans residues 305-357. This rigid core forms a beta-arch that turns at residues (322)CGS(324). Two protofilaments stack together via a long interface that stretches from G323 to I354. Together, these two protofilaments form a four-layered beta-sheet core whose sidechains are stabilized by numerous polar and hydrophobic interactions. This structure gives insight into the fibril morphologies and molecular conformations that can be adopted by this protease-resistant core of AD tau under different pH and ionic conditions.

-	~~Authors: Duan~~, P., Dregni, A.J., ~~Mammeri, N~~.E.~~, Hong, M~~.	+	Structure of the nonhelical filament of the Alzheimer's disease tau core.,Duan P, Dregni AJ, Mammeri NE, Hong M Proc Natl Acad Sci U S A. 2023 Oct 31;120(44):e2310067120. doi: , 10.1073/pnas.2310067120. Epub 2023 Oct 25. PMID:37878719<ref>PMID:37878719</ref>

-	~~Description: Tau (297~~-~~391) in vitro untwisted fibril~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Hong, M~~]]	+	<div class="pdbe-citations 8g58" style="background-color:#fffaf0;"></div>
-	[[Category: Duan, P]]	+	== References ==
-	[[Category: ~~Mammeri, N.E~~]]	+	<references/>
-	[[Category: ~~Dregni, A.J~~]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Dregni AJ]]
		+	[[Category: Duan P]]
		+	[[Category: Hong M]]
		+	[[Category: Mammeri NE]]

OCA at 04:28, 2 March 2023

2023-03-02T04:28:08Z

←Older revision		Revision as of 04:28, 2 March 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8g58 is ON HOLD	+	The entry 8g58 is ON HOLD until Paper Publication

	Authors: Duan, P., Dregni, A.J., Mammeri, N.E., Hong, M.		Authors: Duan, P., Dregni, A.J., Mammeri, N.E., Hong, M.
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	Description: Tau (297-391) in vitro untwisted fibril		Description: Tau (297-391) in vitro untwisted fibril
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Dregni, A.J]]
	[[Category: Hong, M]]		[[Category: Hong, M]]
-	[[Category: Mammeri, N.E]]
	[[Category: Duan, P]]		[[Category: Duan, P]]
		+	[[Category: Mammeri, N.E]]
		+	[[Category: Dregni, A.J]]

OCA: Protected "8g58" [edit=sysop:move=sysop]

2023-02-22T10:20:10Z

Protected "8g58" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:20, 22 February 2023

OCA: New page: '''Unreleased structure''' The entry 8g58 is ON HOLD Authors: Duan, P., Dregni, A.J., Mammeri, N.E., Hong, M. Description: Tau (297-391) in vitro untwisted fibril [[Category: Unrelease...

2023-02-22T10:20:07Z

New page: '''Unreleased structure''' The entry 8g58 is ON HOLD Authors: Duan, P., Dregni, A.J., Mammeri, N.E., Hong, M. Description: Tau (297-391) in vitro untwisted fibril [[Category: Unrelease...

New page

'''Unreleased structure'''

The entry 8g58 is ON HOLD

Authors: Duan, P., Dregni, A.J., Mammeri, N.E., Hong, M.

Description: Tau (297-391) in vitro untwisted fibril
[[Category: Unreleased Structures]]
[[Category: Dregni, A.J]]
[[Category: Hong, M]]
[[Category: Mammeri, N.E]]
[[Category: Duan, P]]

8g58 - Revision history

OCA at 11:59, 8 November 2023

OCA at 04:28, 2 March 2023

OCA: Protected "8g58" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8g58 is ON HOLD Authors: Duan, P., Dregni, A.J., Mammeri, N.E., Hong, M. Description: Tau (297-391) in vitro untwisted fibril [[Category: Unrelease...