2n0a: Difference between revisions

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==Atomic-resolution structure of alpha-synuclein fibrils==
==Atomic-resolution structure of alpha-synuclein fibrils==
<StructureSection load='2n0a' size='340' side='right'caption='[[2n0a]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''>
<StructureSection load='2n0a' size='340' side='right'caption='[[2n0a]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2n0a]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N0A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N0A FirstGlance]. <br>
<table><tr><td colspan='2'>[[2n0a]] 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=2N0A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N0A FirstGlance]. <br>
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SNCA, NACP, PARK1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2n0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n0a OCA], [https://pdbe.org/2n0a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n0a RCSB], [https://www.ebi.ac.uk/pdbsum/2n0a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n0a 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=2n0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n0a OCA], [https://pdbe.org/2n0a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n0a RCSB], [https://www.ebi.ac.uk/pdbsum/2n0a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n0a ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== 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.  
[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 ==
[[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.  
[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.
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== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Berthold, D A]]
[[Category: Berthold DA]]
[[Category: Comellas, G]]
[[Category: Comellas G]]
[[Category: Courtney, J M]]
[[Category: Courtney JM]]
[[Category: Covell, D J]]
[[Category: Covell DJ]]
[[Category: George, J M]]
[[Category: George JM]]
[[Category: Kim, J K]]
[[Category: Kim JK]]
[[Category: Kloepper, K D]]
[[Category: Kloepper KD]]
[[Category: Lee, V M]]
[[Category: Lee VM]]
[[Category: Nieuwkoop, A J]]
[[Category: Nieuwkoop AJ]]
[[Category: Rienstra, C M]]
[[Category: Rienstra CM]]
[[Category: Schwieters, C D]]
[[Category: Schwieters CD]]
[[Category: Tuttle, M D]]
[[Category: Tuttle MD]]
[[Category: Amyloid]]
[[Category: Parkinson's disease]]
[[Category: Protein fibril]]
[[Category: Structural protein]]

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