Alpha-synuclein

From Proteopedia

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spinqualitylabelsall models Human alpha-synuclein (PDB 6flt) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Contents 1 Function 2 Disease 3 Relevance 4 Structural highlights Function Alpha-Synuclein (Syn) is a human neuronal protein which has several roles in synaptic activity. Syn enhances vesicle priming, fusion and dilation of exocytotic pores[1]. Syn associates with the dopamine transporter and modulates its activity[2]. Disease Syn is a central component in the pathogenicity of Parkinson Disease (PD). PD is associated with deposition of Syn in the form of Lewy bodies throughout the brain and loss of dopaminergic neuronal cells[3]. Relevance Various therapeutic approaches are investigated such as blocking of Syn receptors and searching for small molecules to target Syn aggregation and increase its degradation by increasing [4]. Structural highlights

3D Structures of alpha-synuclein

Updated on 04-April-2020

6flt, 6h6b, 6a6b, 6cu7, 6cu8, 6rt0, 6rtb, 6sst, 6ssx, 6xyo, 6xyp, 6xyq, 6osj, 6osl, 6osm – hSyn – human - Cryo EM
2n0a – hSyn – NMR
6ufr, 6peo, 6pes – hSyn (mutant) - Cryo EM
2m55 – hSyn residues 1-19 + calmodulin – NMR
6i42 – hSyn residues 48-60 + cyclophilin A
5crw – hSyn residues 31-41 + protein disulfide isomerase
6ct7 – hSyn residues 1-10 + antibody
2x6m – hSyn residues 132-140 + antibody
3q25, 3q26, 3q27, 3q28, 3q29 – hSyn peptide/MBP
3q26 – hSyn residues 10-42/MBP

References

1. ↑ PMID:28288128/ref>. Syn acts as a molecular chaperone in assisting the folding of SNAREs - the synaptic fusion components<ref>PMID:20798282</li> <li id="cite_note-1">[[#cite_ref-1|↑]] Butler B, Saha K, Rana T, Becker JP, Sambo D, Davari P, Goodwin JS, Khoshbouei H. Dopamine Transporter Activity Is Modulated by alpha-Synuclein. J Biol Chem. 2015 Dec 4;290(49):29542-54. doi: 10.1074/jbc.M115.691592. Epub 2015, Oct 6. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/26442590 26442590] doi:[http://dx.doi.org/10.1074/jbc.M115.691592 http://dx.doi.org/10.1074/jbc.M115.691592]</li> <li id="cite_note-2">[[#cite_ref-2|↑]] Xu L, Pu J. Alpha-Synuclein in Parkinson's Disease: From Pathogenetic Dysfunction to Potential Clinical Application. Parkinsons Dis. 2016;2016:1720621. doi: 10.1155/2016/1720621. Epub 2016 Aug 17. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/27610264 27610264] doi:[http://dx.doi.org/10.1155/2016/1720621 http://dx.doi.org/10.1155/2016/1720621]</li> <li id="cite_note-3">[[#cite_ref-3|↑]] Fields CR, Bengoa-Vergniory N, Wade-Martins R. Targeting Alpha-Synuclein as a Therapy for Parkinson's Disease. Front Mol Neurosci. 2019 Dec 5;12:299. doi: 10.3389/fnmol.2019.00299. eCollection, 2019. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/31866823 31866823] doi:[http://dx.doi.org/10.3389/fnmol.2019.00299 http://dx.doi.org/10.3389/fnmol.2019.00299]</li></ol></ref>