Alpha-synuclein: Difference between revisions
Michal Harel (talk | contribs) New page: <StructureSection load='6flt' size='340' side='right' caption='Human alpha-synuclein (PDB 6flt)' scene=''> == Function == '''Alpha-Synuclein''' (Syn) is a human neuronal protein whi... |
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<StructureSection load='6flt' size='340' side='right' caption='Human alpha-synuclein (PDB [[6flt]])' scene=''> | <StructureSection load='6flt' size='340' side='right' caption='Human alpha-synuclein (PDB [[6flt]])' scene=''> | ||
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== Structural highlights == | == Structural highlights == | ||
The Syn structure shows 8 β-sheet forming segments interrupted by Gly residues. Seven PD-associated familial mutations are known. The 3D structure shows a hydrophobic cleft which can provide an entry point for an incoming Syn molecule elongating the fibril<ref>PMID:29969391</ref>. | |||
</StructureSection> | </StructureSection> | ||
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[[3q25]], [[3q26]], [[3q27]], [[3q28]], [[3q29]] – hSyn peptide/MBP<br /> | [[3q25]], [[3q26]], [[3q27]], [[3q28]], [[3q29]] – hSyn peptide/MBP<br /> | ||
[[3q26]] – hSyn residues 10-42/MBP<br /> | [[3q26]] – hSyn residues 10-42/MBP<br /> | ||
[[4r0u]], [[4r0w]], [[4rik]], [[4ril]] - hSyn amyloid-forming peptide<br /> | |||
[[4znn]] - hSyn amyloid-forming peptide (mutant)<br /> | |||
== References == | == References == | ||
Revision as of 12:11, 4 April 2020
FunctionAlpha-Synuclein (Syn) is a human neuronal protein which has several roles in synaptic activity. Syn enhances vesicle priming, fusion and dilation of exocytotic poresCite error: Closing DiseaseSyn 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[2]. RelevanceVarious 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 [3]. Structural highlightsThe Syn structure shows 8 β-sheet forming segments interrupted by Gly residues. Seven PD-associated familial mutations are known. The 3D structure shows a hydrophobic cleft which can provide an entry point for an incoming Syn molecule elongating the fibril[4].
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3D Structures of alpha-synuclein3D 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
4r0u, 4r0w, 4rik, 4ril - hSyn amyloid-forming peptide
4znn - hSyn amyloid-forming peptide (mutant)
ReferencesReferences
- ↑ 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