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 acts as a molecular chaperone in assisting the folding of SNAREs - the synaptic fusion components[2]. Syn associates with the dopamine transporter and modulates its activity[3].
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[4].
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 [5].
Structural highlights
The Syn structure shows forming segments interrupted by . Seven PD-associated familial are known. The 3D structure shows a which can provide an entry point for an incoming Syn molecule elongating the fibril[6].
3D Structures of alpha-synuclein
Alpha-synuclein 3D structures
Updated on 24-September-2024
6h6b, 6a6b, 6cu7, 6cu8, 6l1t, 6l1u, 6l4s, 6lrq,6rt0, 6rtb, 6sst, 6ssx, 6xyo, 6xyp, 6xyq, 6osj, 6osl, 6osm, 7c1d, 7l7h, 7nca, 7ncg, 7nch, 7nci, 7ncj, 7nck, 7ozg, 7ozh, 7v47, 7v48, 7v4a, 7v4b, 7v4c, 7v4d, 8a4l – hSyn – human - Cryo EM
2n0a – hSyn – NMR
6ufr, 6peo, 6pes, 7e0f – hSyn (mutant) - Cryo EM
7lc9 – hSyn 41-140 - Cryo EM
8a9l – hSyn + peptide - Cryo EM
7stx – hSyn + acetyltransferase + CoA - 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
4r0u, 4r0w, 4rik, 4ril - hSyn amyloid-forming peptide
4znn - hSyn amyloid-forming peptide (mutant)
References
- ↑ Logan T, Bendor J, Toupin C, Thorn K, Edwards RH. alpha-Synuclein promotes dilation of the exocytotic fusion pore. Nat Neurosci. 2017 May;20(5):681-689. doi: 10.1038/nn.4529. Epub 2017 Mar 13. PMID:28288128 doi:http://dx.doi.org/10.1038/nn.4529
- ↑ Burre J, Sharma M, Tsetsenis T, Buchman V, Etherton MR, Sudhof TC. Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro. Science. 2010 Sep 24;329(5999):1663-7. doi: 10.1126/science.1195227. Epub 2010, Aug 26. PMID:20798282 doi:http://dx.doi.org/10.1126/science.1195227
- ↑ 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:26442590 doi:http://dx.doi.org/10.1074/jbc.M115.691592
- ↑ 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:27610264 doi:http://dx.doi.org/10.1155/2016/1720621
- ↑ 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:31866823 doi:http://dx.doi.org/10.3389/fnmol.2019.00299
- ↑ Guerrero-Ferreira R, Taylor NMI, Mona D, Ringler P, Lauer ME, Riek R, Britschgi M, Stahlberg H. Cryo-EM structure of alpha-synuclein fibrils. Elife. 2018 Jul 3;7. pii: 36402. doi: 10.7554/eLife.36402. PMID:29969391 doi:http://dx.doi.org/10.7554/eLife.36402
