6ufr - Revision history

OCA at 09:29, 20 March 2024

2024-03-20T09:29:31Z

←Older revision		Revision as of 09:29, 20 March 2024
Line 3:		Line 3:
	<SX load='6ufr' size='340' side='right' viewer='molstar' caption='[[6ufr]], [[Resolution\|resolution]] 2.50Å' scene=''>		<SX load='6ufr' size='340' side='right' viewer='molstar' caption='[[6ufr]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ufr]] is a 10 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=6UFR OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6UFR FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ufr]] is a 10 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=6UFR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UFR FirstGlance]. <br>
-	</td></tr><tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~SNCA~~, ~~NACP, PARK1 (~~[~~http://www~~.~~ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=~~5&~~id=9606 HUMAN])~~</td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 2.5Å</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6ufr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ufr OCA], [~~http~~://pdbe.org/6ufr PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6ufr RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6ufr PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6ufr 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=6ufr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ufr OCA], [https://pdbe.org/6ufr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ufr RCSB], [https://www.ebi.ac.uk/pdbsum/6ufr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ufr ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/SYUA_HUMAN SYUA_HUMAN]] Note=Genetic alterations of SNCA resulting in aberrant polymerization into fibrils, are associated with several neurodegenerative diseases (synucleinopathies). SNCA fibrillar aggregates represent the major non A-beta component of Alzheimer disease amyloid plaque, and a major component of Lewy body inclusions. They are also found within Lewy body (LB)-like intraneuronal inclusions, glial inclusions and axonal spheroids in neurodegeneration with brain iron accumulation type 1. Defects in SNCA are the cause of Parkinson disease type 1 (PARK1) [MIM:[~~http~~://omim.org/entry/168601 168601]]. A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features.<ref>PMID:9197268</ref> <ref>PMID:9462735</ref> <ref>PMID:14755719</ref> Defects in SNCA are the cause of Parkinson disease type 4 (PARK4) [MIM:[~~http~~://omim.org/entry/605543 605543]]. A complex neurodegenerative disorder with manifestations ranging from typical Parkinson disease to dementia with Lewy bodies. Clinical features include parkinsonian symptoms (tremor, rigidity, postural instability and bradykinesia), dementia, diffuse Lewy body pathology, autonomic dysfunction, hallucinations and paranoia. Defects in SNCA are the cause of dementia Lewy body (DLB) [MIM:[~~http~~://omim.org/entry/127750 127750]]. A neurodegenerative disorder clinically characterized by mental impairment leading to dementia, parkinsonism, often with fluctuating cognitive function, visual hallucinations, falls, syncopal episodes, and sensitivity to neuroleptic medication. Brainstem or cortical intraneuronal accumulations of aggregated proteins (Lewy bodies) are the only essential pathologic features. Patients may also have hippocampal and neocortical senile plaques, sometimes in sufficient number to fulfill the diagnostic criteria for Alzheimer disease.	+	[https://www.uniprot.org/uniprot/SYUA_HUMAN SYUA_HUMAN] Note=Genetic alterations of SNCA resulting in aberrant polymerization into fibrils, are associated with several neurodegenerative diseases (synucleinopathies). SNCA fibrillar aggregates represent the major non A-beta component of Alzheimer disease amyloid plaque, and a major component of Lewy body inclusions. They are also found within Lewy body (LB)-like intraneuronal inclusions, glial inclusions and axonal spheroids in neurodegeneration with brain iron accumulation type 1. Defects in SNCA are the cause of Parkinson disease type 1 (PARK1) [MIM:[https://omim.org/entry/168601 168601]. A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features.<ref>PMID:9197268</ref> <ref>PMID:9462735</ref> <ref>PMID:14755719</ref> Defects in SNCA are the cause of Parkinson disease type 4 (PARK4) [MIM:[https://omim.org/entry/605543 605543]. A complex neurodegenerative disorder with manifestations ranging from typical Parkinson disease to dementia with Lewy bodies. Clinical features include parkinsonian symptoms (tremor, rigidity, postural instability and bradykinesia), dementia, diffuse Lewy body pathology, autonomic dysfunction, hallucinations and paranoia. Defects in SNCA are the cause of dementia Lewy body (DLB) [MIM:[https://omim.org/entry/127750 127750]. A neurodegenerative disorder clinically characterized by mental impairment leading to dementia, parkinsonism, often with fluctuating cognitive function, visual hallucinations, falls, syncopal episodes, and sensitivity to neuroleptic medication. Brainstem or cortical intraneuronal accumulations of aggregated proteins (Lewy bodies) are the only essential pathologic features. Patients may also have hippocampal and neocortical senile plaques, sometimes in sufficient number to fulfill the diagnostic criteria for Alzheimer disease.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/SYUA_HUMAN SYUA_HUMAN]] May be involved in the regulation of dopamine release and transport. Induces fibrillization of microtubule-associated protein tau. Reduces neuronal responsiveness to various apoptotic stimuli, leading to a decreased caspase-3 activation.	+	[https://www.uniprot.org/uniprot/SYUA_HUMAN SYUA_HUMAN] May be involved in the regulation of dopamine release and transport. Induces fibrillization of microtubule-associated protein tau. Reduces neuronal responsiveness to various apoptotic stimuli, leading to a decreased caspase-3 activation.
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Aggregation of alpha-synuclein is a defining molecular feature of Parkinson's disease, Lewy body dementia, and multiple systems atrophy. Hereditary mutations in alpha-synuclein are linked to both Parkinson's disease and Lewy body dementia; in particular, patients bearing the E46K disease mutation manifest a clinical picture of parkinsonism and Lewy body dementia, and E46K creates more pathogenic fibrils in vitro. Understanding the effect of these hereditary mutations on alpha-synuclein fibril structure is fundamental to alpha-synuclein biology. We therefore determined the cryo-electron microscopy (cryo-EM) structure of alpha-synuclein fibrils containing the hereditary E46K mutation. The 2.5-A structure reveals a symmetric double protofilament in which the molecules adopt a vastly rearranged, lower energy fold compared to wild-type fibrils. We propose that the E46K misfolding pathway avoids electrostatic repulsion between K46 and K80, a residue pair which form the E46-K80 salt bridge in the wild-type fibril structure. We hypothesize that, under our conditions, the wild-type fold does not reach this deeper energy well of the E46K fold because the E46-K80 salt bridge diverts alpha-synuclein into a kinetic trap-a shallower, more accessible energy minimum. The E46K mutation apparently unlocks a more stable and pathogenic fibril structure.	+
-		+
-	The alpha-synuclein hereditary mutation E46K unlocks a more stable, pathogenic fibril structure.,Boyer DR, Li B, Sun C, Fan W, Zhou K, Hughes MP, Sawaya MR, Jiang L, Eisenberg DS Proc Natl Acad Sci U S A. 2020 Feb 3. pii: 1917914117. doi:, 10.1073/pnas.1917914117. PMID:32015135<ref>PMID:32015135</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 6ufr" style="background-color:#fffaf0;"></div>~~	+

	==See Also==		==See Also==
Line 27:		Line 18:
	__TOC__		__TOC__
	</SX>		</SX>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Boyer~~, D R~~]]	+	[[Category: Boyer DR]]
-	[[Category: Eisenberg~~, D S~~]]	+	[[Category: Eisenberg DS]]
-	[[Category: Jiang, L]]	+	[[Category: Jiang L]]
-	[[Category: Li, B]]	+	[[Category: Li B]]
-	[[Category: Sawaya~~, M R]]~~	+	[[Category: Sawaya MR]]
-	~~[[Category: Alpha-synuclein]]~~	+
-	~~[[Category: Amyloid]]~~	+
-	~~[[Category: E46k]]~~	+
-	~~[[Category: Fibril]]~~	+
-	~~[[Category: Hereditary mutation]]~~	+
-	~~[[Category: Lewy body dementia]]~~	+
-	~~[[Category: Parkinson's disease]]~~	+
-	~~[[Category: Protein fibril~~]]	+

OCA at 06:47, 11 April 2020

2020-04-11T06:47:38Z

←Older revision		Revision as of 06:47, 11 April 2020
Line 3:		Line 3:
	<SX load='6ufr' size='340' side='right' viewer='molstar' caption='[[6ufr]], [[Resolution\|resolution]] 2.50Å' scene=''>		<SX load='6ufr' size='340' side='right' viewer='molstar' caption='[[6ufr]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ufr]] is a 10 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=6UFR OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6UFR FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ufr]] is a 10 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=6UFR OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6UFR FirstGlance]. <br>
	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SNCA, NACP, PARK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SNCA, NACP, PARK1 ([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=6ufr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ufr OCA], [http://pdbe.org/6ufr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ufr RCSB], [http://www.ebi.ac.uk/pdbsum/6ufr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ufr ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6ufr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ufr OCA], [http://pdbe.org/6ufr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ufr RCSB], [http://www.ebi.ac.uk/pdbsum/6ufr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ufr ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 6ufr" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6ufr" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Alpha-synuclein\|Alpha-synuclein]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 01:10, 7 March 2020

2020-03-07T01:10:12Z

←Older revision		Revision as of 01:10, 7 March 2020
Line 1:		Line 1:

	==Structure of recombinantly assembled E46K alpha-synuclein fibrils==		==Structure of recombinantly assembled E46K alpha-synuclein fibrils==
-	<~~StructureSection~~ load='6ufr' size='340' side='right'caption='[[6ufr]], [[Resolution\|resolution]] 2.50Å' scene=''>	+	<SX load='6ufr' size='340' side='right' viewer='molstar' caption='[[6ufr]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6ufr]] is a 10 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=6UFR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UFR FirstGlance]. <br>		<table><tr><td colspan='2'>[[6ufr]] is a 10 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=6UFR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UFR FirstGlance]. <br>
Line 23:		Line 23:
	<references/>		<references/>
	__TOC__		__TOC__
-	</~~StructureSection~~>	+	</SX>
	[[Category: Human]]		[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]

OCA at 10:33, 26 February 2020

2020-02-26T10:33:31Z

←Older revision		Revision as of 10:33, 26 February 2020
Line 3:		Line 3:
	<StructureSection load='6ufr' size='340' side='right'caption='[[6ufr]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='6ufr' size='340' side='right'caption='[[6ufr]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ufr]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UFR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UFR FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ufr]] is a 10 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=6UFR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UFR FirstGlance]. <br>
-	</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=6ufr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ufr OCA], [http://pdbe.org/6ufr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ufr RCSB], [http://www.ebi.ac.uk/pdbsum/6ufr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ufr ProSAT]</span></td></tr>	+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SNCA, NACP, PARK1 ([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=6ufr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ufr OCA], [http://pdbe.org/6ufr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ufr RCSB], [http://www.ebi.ac.uk/pdbsum/6ufr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ufr ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Boyer, D R]]		[[Category: Boyer, D R]]

OCA at 06:42, 19 February 2020

2020-02-19T06:42:43Z

←Older revision		Revision as of 06:42, 19 February 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6ufr is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Structure of recombinantly assembled E46K alpha-synuclein fibrils==
		+	<StructureSection load='6ufr' size='340' side='right'caption='[[6ufr]], [[Resolution\|resolution]] 2.50Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6ufr]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UFR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UFR FirstGlance]. <br>
		+	</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=6ufr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ufr OCA], [http://pdbe.org/6ufr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ufr RCSB], [http://www.ebi.ac.uk/pdbsum/6ufr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ufr ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/SYUA_HUMAN SYUA_HUMAN]] Note=Genetic alterations of SNCA resulting in aberrant polymerization into fibrils, are associated with several neurodegenerative diseases (synucleinopathies). SNCA fibrillar aggregates represent the major non A-beta component of Alzheimer disease amyloid plaque, and a major component of Lewy body inclusions. They are also found within Lewy body (LB)-like intraneuronal inclusions, glial inclusions and axonal spheroids in neurodegeneration with brain iron accumulation type 1. Defects in SNCA are the cause of Parkinson disease type 1 (PARK1) [MIM:[http://omim.org/entry/168601 168601]]. A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features.<ref>PMID:9197268</ref> <ref>PMID:9462735</ref> <ref>PMID:14755719</ref> Defects in SNCA are the cause of Parkinson disease type 4 (PARK4) [MIM:[http://omim.org/entry/605543 605543]]. A complex neurodegenerative disorder with manifestations ranging from typical Parkinson disease to dementia with Lewy bodies. Clinical features include parkinsonian symptoms (tremor, rigidity, postural instability and bradykinesia), dementia, diffuse Lewy body pathology, autonomic dysfunction, hallucinations and paranoia. Defects in SNCA are the cause of dementia Lewy body (DLB) [MIM:[http://omim.org/entry/127750 127750]]. A neurodegenerative disorder clinically characterized by mental impairment leading to dementia, parkinsonism, often with fluctuating cognitive function, visual hallucinations, falls, syncopal episodes, and sensitivity to neuroleptic medication. Brainstem or cortical intraneuronal accumulations of aggregated proteins (Lewy bodies) are the only essential pathologic features. Patients may also have hippocampal and neocortical senile plaques, sometimes in sufficient number to fulfill the diagnostic criteria for Alzheimer disease.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/SYUA_HUMAN SYUA_HUMAN]] May be involved in the regulation of dopamine release and transport. Induces fibrillization of microtubule-associated protein tau. Reduces neuronal responsiveness to various apoptotic stimuli, leading to a decreased caspase-3 activation.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Aggregation of alpha-synuclein is a defining molecular feature of Parkinson's disease, Lewy body dementia, and multiple systems atrophy. Hereditary mutations in alpha-synuclein are linked to both Parkinson's disease and Lewy body dementia; in particular, patients bearing the E46K disease mutation manifest a clinical picture of parkinsonism and Lewy body dementia, and E46K creates more pathogenic fibrils in vitro. Understanding the effect of these hereditary mutations on alpha-synuclein fibril structure is fundamental to alpha-synuclein biology. We therefore determined the cryo-electron microscopy (cryo-EM) structure of alpha-synuclein fibrils containing the hereditary E46K mutation. The 2.5-A structure reveals a symmetric double protofilament in which the molecules adopt a vastly rearranged, lower energy fold compared to wild-type fibrils. We propose that the E46K misfolding pathway avoids electrostatic repulsion between K46 and K80, a residue pair which form the E46-K80 salt bridge in the wild-type fibril structure. We hypothesize that, under our conditions, the wild-type fold does not reach this deeper energy well of the E46K fold because the E46-K80 salt bridge diverts alpha-synuclein into a kinetic trap-a shallower, more accessible energy minimum. The E46K mutation apparently unlocks a more stable and pathogenic fibril structure.

-	~~Authors~~:	+	The alpha-synuclein hereditary mutation E46K unlocks a more stable, pathogenic fibril structure.,Boyer DR, Li B, Sun C, Fan W, Zhou K, Hughes MP, Sawaya MR, Jiang L, Eisenberg DS Proc Natl Acad Sci U S A. 2020 Feb 3. pii: 1917914117. doi:, 10.1073/pnas.1917914117. PMID:32015135<ref>PMID:32015135</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6ufr" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Boyer, D R]]
		+	[[Category: Eisenberg, D S]]
		+	[[Category: Jiang, L]]
		+	[[Category: Li, B]]
		+	[[Category: Sawaya, M R]]
		+	[[Category: Alpha-synuclein]]
		+	[[Category: Amyloid]]
		+	[[Category: E46k]]
		+	[[Category: Fibril]]
		+	[[Category: Hereditary mutation]]
		+	[[Category: Lewy body dementia]]
		+	[[Category: Parkinson's disease]]
		+	[[Category: Protein fibril]]

OCA at 04:33, 16 October 2019

2019-10-16T04:33:16Z

←Older revision		Revision as of 04:33, 16 October 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6ufr is ON HOLD	+	The entry 6ufr is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6ufr" [edit=sysop:move=sysop]

2019-10-02T08:47:23Z

Protected "6ufr" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:47, 2 October 2019

OCA: New page: '''Unreleased structure''' The entry 6ufr is ON HOLD Authors: Description: Category: Unreleased Structures

2019-10-02T08:47:21Z

New page: '''Unreleased structure''' The entry 6ufr is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6ufr is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]