4bxl - Revision history

OCA at 17:14, 7 September 2022

OCA — Wed, 07 Sep 2022 17:14:59 GMT

←Older revision		Revision as of 17:14, 7 September 2022
Line 1:		Line 1:

	==Structure of alpha-synuclein in complex with an engineered binding protein==		==Structure of alpha-synuclein in complex with an engineered binding protein==
-	<StructureSection load='4bxl' size='340' side='right'caption='[[4bxl~~]], [[NMR_Ensembles_of_Models \| 10 NMR models~~]]' scene=''>	+	<StructureSection load='4bxl' size='340' side='right'caption='[[4bxl]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4bxl]] is a 3 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~] and [~~http~~://en.wikipedia.org/wiki/~~Synthetic_construct_sequences~~ Synthetic construct ~~sequences~~]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BXL OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4BXL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4bxl]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BXL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BXL 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=4bxl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bxl OCA], [~~http~~://pdbe.org/4bxl PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4bxl RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4bxl PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4bxl ProSAT]</span></td></tr>	+	</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=4bxl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bxl OCA], [https://pdbe.org/4bxl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bxl RCSB], [https://www.ebi.ac.uk/pdbsum/4bxl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bxl 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 ==~~	+
-	The misfolding and aggregation of the protein alpha-synuclein (alpha-syn), which results in the formation of amyloid fibrils, is involved in the pathogenesis of Parkinson's disease and other synucleinopathies. The emergence of amyloid toxicity is associated with the formation of partially folded aggregation intermediates. Here, we engineered a class of binding proteins termed beta-wrapins (beta-wrap proteins) with affinity for alpha-synuclein (alpha-syn). The NMR structure of an alpha-syn:beta-wrapin complex reveals a beta-hairpin of alpha-syn comprising the sequence region alpha-syn(37-54). The beta-wrapin inhibits alpha-syn aggregation and toxicity at substoichiometric concentrations, demonstrating that it interferes with the nucleation of aggregation.	+
-		+
-	Sequestration of a beta-Hairpin for Control of alpha-Synuclein Aggregation.,Mirecka EA, Shaykhalishahi H, Gauhar A, Akgul S, Lecher J, Willbold D, Stoldt M, Hoyer W Angew Chem Int Ed Engl. 2014 Apr 14;53(16):4227-30. doi: 10.1002/anie.201309001. , Epub 2014 Mar 12. PMID:24623599<ref>PMID:24623599</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 4bxl" style="background-color:#fffaf0;"></div>~~	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Synthetic construct ~~sequences~~]]	+	[[Category: Synthetic construct]]
-	[[Category: Hoyer, W]]	+	[[Category: Hoyer W]]
-	[[Category: Lecher, J]]	+	[[Category: Lecher J]]
-	[[Category: Mirecka~~, E A~~]]	+	[[Category: Mirecka EA]]
-	[[Category: Shaykhalishahi, H]]	+	[[Category: Shaykhalishahi H]]
-	[[Category: Stoldt, M]]	+	[[Category: Stoldt M]]
-	~~[[Category: Amyloid]]~~	+
-	~~[[Category: Fibril]]~~	+
-	~~[[Category: Parkinson's disease]]~~	+
-	~~[[Category: Protein aggregation]]~~	+
-	~~[[Category: Protein engineering]]~~	+
-	~~[[Category: Protein misfolding]]~~	+
-	~~[[Category: Scaffold protein~~]]	+

OCA at 13:31, 13 March 2019

OCA — Wed, 13 Mar 2019 13:31:51 GMT

←Older revision		Revision as of 13:31, 13 March 2019
Line 1:		Line 1:

	==Structure of alpha-synuclein in complex with an engineered binding protein==		==Structure of alpha-synuclein in complex with an engineered binding protein==
-	<StructureSection load='4bxl' size='340' side='right' caption='[[4bxl]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>	+	<StructureSection load='4bxl' size='340' side='right'caption='[[4bxl]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4bxl]] is a 3 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BXL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BXL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4bxl]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BXL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BXL 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=4bxl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bxl OCA], [http://pdbe.org/4bxl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bxl RCSB], [http://www.ebi.ac.uk/pdbsum/4bxl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bxl ProSAT]</span></td></tr>		</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=4bxl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bxl OCA], [http://pdbe.org/4bxl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bxl RCSB], [http://www.ebi.ac.uk/pdbsum/4bxl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bxl ProSAT]</span></td></tr>
	</table>		</table>
Line 23:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
		+	[[Category: Synthetic construct sequences]]
	[[Category: Hoyer, W]]		[[Category: Hoyer, W]]
	[[Category: Lecher, J]]		[[Category: Lecher, J]]

OCA at 11:09, 11 August 2016

OCA — Thu, 11 Aug 2016 11:09:52 GMT

←Older revision		Revision as of 11:09, 11 August 2016
Line 1:		Line 1:
		+
	==Structure of alpha-synuclein in complex with an engineered binding protein==		==Structure of alpha-synuclein in complex with an engineered binding protein==
	<StructureSection load='4bxl' size='340' side='right' caption='[[4bxl]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>		<StructureSection load='4bxl' size='340' side='right' caption='[[4bxl]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4bxl]] is a 3 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BXL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BXL FirstGlance]. <br>		<table><tr><td colspan='2'>[[4bxl]] is a 3 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BXL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BXL 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=4bxl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bxl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bxl RCSB], [http://www.ebi.ac.uk/pdbsum/4bxl PDBsum]</span></td></tr>	+	</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=4bxl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bxl OCA], [http://pdbe.org/4bxl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bxl RCSB], [http://www.ebi.ac.uk/pdbsum/4bxl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bxl ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 17:		Line 18:
	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 4bxl" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 12:58, 4 January 2015

OCA — Sun, 04 Jan 2015 12:58:51 GMT

←Older revision		Revision as of 12:58, 4 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4bxl]] is a 3 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BXL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BXL FirstGlance]. <br>		<table><tr><td colspan='2'>[[4bxl]] is a 3 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BXL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BXL FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4bxl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bxl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bxl RCSB], [http://www.ebi.ac.uk/pdbsum/4bxl PDBsum]</span></td></tr>	+	</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=4bxl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bxl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bxl RCSB], [http://www.ebi.ac.uk/pdbsum/4bxl PDBsum]</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.		[[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.
Line 15:		Line 15:
	Sequestration of a beta-Hairpin for Control of alpha-Synuclein Aggregation.,Mirecka EA, Shaykhalishahi H, Gauhar A, Akgul S, Lecher J, Willbold D, Stoldt M, Hoyer W Angew Chem Int Ed Engl. 2014 Apr 14;53(16):4227-30. doi: 10.1002/anie.201309001. , Epub 2014 Mar 12. PMID:24623599<ref>PMID:24623599</ref>		Sequestration of a beta-Hairpin for Control of alpha-Synuclein Aggregation.,Mirecka EA, Shaykhalishahi H, Gauhar A, Akgul S, Lecher J, Willbold D, Stoldt M, Hoyer W Angew Chem Int Ed Engl. 2014 Apr 14;53(16):4227-30. doi: 10.1002/anie.201309001. , Epub 2014 Mar 12. PMID:24623599<ref>PMID:24623599</ref>

-	From ~~MEDLINEÂ®~~/~~PubMedÂ®~~, 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>
	== References ==		== References ==
Line 21:		Line 21:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Hoyer, W.]]	+	[[Category: Hoyer, W]]
-	[[Category: Lecher, J.]]	+	[[Category: Lecher, J]]
-	[[Category: Mirecka, E A.]]	+	[[Category: Mirecka, E A]]
-	[[Category: Shaykhalishahi, H.]]	+	[[Category: Shaykhalishahi, H]]
-	[[Category: Stoldt, M.]]	+	[[Category: Stoldt, M]]
	[[Category: Amyloid]]		[[Category: Amyloid]]
	[[Category: Fibril]]		[[Category: Fibril]]

OCA at 09:01, 21 May 2014

OCA — Wed, 21 May 2014 09:01:05 GMT

←Older revision		Revision as of 09:01, 21 May 2014
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Structure of alpha-synuclein in complex with an engineered binding protein==
		+	<StructureSection load='4bxl' size='340' side='right' caption='[[4bxl]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4bxl]] is a 3 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BXL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BXL FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4bxl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bxl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bxl RCSB], [http://www.ebi.ac.uk/pdbsum/4bxl PDBsum]</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 ==
		+	The misfolding and aggregation of the protein alpha-synuclein (alpha-syn), which results in the formation of amyloid fibrils, is involved in the pathogenesis of Parkinson's disease and other synucleinopathies. The emergence of amyloid toxicity is associated with the formation of partially folded aggregation intermediates. Here, we engineered a class of binding proteins termed beta-wrapins (beta-wrap proteins) with affinity for alpha-synuclein (alpha-syn). The NMR structure of an alpha-syn:beta-wrapin complex reveals a beta-hairpin of alpha-syn comprising the sequence region alpha-syn(37-54). The beta-wrapin inhibits alpha-syn aggregation and toxicity at substoichiometric concentrations, demonstrating that it interferes with the nucleation of aggregation.

-	~~The entry 4bxl is ON HOLD until Paper Publication~~	+	Sequestration of a beta-Hairpin for Control of alpha-Synuclein Aggregation.,Mirecka EA, Shaykhalishahi H, Gauhar A, Akgul S, Lecher J, Willbold D, Stoldt M, Hoyer W Angew Chem Int Ed Engl. 2014 Apr 14;53(16):4227-30. doi: 10.1002/anie.201309001. , Epub 2014 Mar 12. PMID:24623599<ref>PMID:24623599</ref>

-	~~Authors: MIRECKA~~, E.A., ~~SHAYKHALISHAHI, H~~.~~, LECHER~~, J., ~~STOLDT~~, M., ~~HOYER, W~~.	+	From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~Structure of alpha-synuclein in complex with an engineered binding~~ protein	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Hoyer, W.]]
		+	[[Category: Lecher, J.]]
		+	[[Category: Mirecka, E A.]]
		+	[[Category: Shaykhalishahi, H.]]
		+	[[Category: Stoldt, M.]]
		+	[[Category: Amyloid]]
		+	[[Category: Fibril]]
		+	[[Category: Parkinson's disease]]
		+	[[Category: Protein aggregation]]
		+	[[Category: Protein engineering]]
		+	[[Category: Protein misfolding]]
		+	[[Category: Scaffold protein]]

OCA at 19:42, 7 August 2013

OCA — Wed, 07 Aug 2013 19:42:21 GMT

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	Authors: MIRECKA, E.A., SHAYKHALISHAHI, H., LECHER, J., STOLDT, M., HOYER, W.		Authors: MIRECKA, E.A., SHAYKHALISHAHI, H., LECHER, J., STOLDT, M., HOYER, W.

	Description: Structure of alpha-synuclein in complex with an engineered binding protein		Description: Structure of alpha-synuclein in complex with an engineered binding protein

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

OCA — Wed, 24 Jul 2013 12:02:59 GMT

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

←Older revision

Revision as of 12:02, 24 July 2013

OCA: New page: '''Unreleased structure''' The entry 4bxl is ON HOLD Authors: MIRECKA, E.A., SHAYKHALISHAHI, H., LECHER, J., STOLDT, M., HOYER, W. Description: Structure of alpha-synuclein in complex ...

OCA — Wed, 24 Jul 2013 12:02:58 GMT

New page: '''Unreleased structure''' The entry 4bxl is ON HOLD Authors: MIRECKA, E.A., SHAYKHALISHAHI, H., LECHER, J., STOLDT, M., HOYER, W. Description: Structure of alpha-synuclein in complex ...

New page

'''Unreleased structure'''

The entry 4bxl is ON HOLD

Authors: MIRECKA, E.A., SHAYKHALISHAHI, H., LECHER, J., STOLDT, M., HOYER, W.

Description: Structure of alpha-synuclein in complex with an engineered binding protein