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==Cryo-EM structure of phosphorylated Tyr39 a-synuclein amyloid fibril== | ==Cryo-EM structure of phosphorylated Tyr39 a-synuclein amyloid fibril== | ||
<StructureSection load='6l1t' size='340' side='right'caption='[[6l1t]]' scene=''> | <StructureSection load='6l1t' size='340' side='right'caption='[[6l1t]], [[Resolution|resolution]] 3.22Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6L1T OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6L1T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6L1T FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.22Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></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=6l1t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l1t OCA], [https://pdbe.org/6l1t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6l1t RCSB], [https://www.ebi.ac.uk/pdbsum/6l1t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6l1t ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Posttranslational modifications (PTMs) of alpha-synuclein (alpha-syn), e.g., phosphorylation, play an important role in modulating alpha-syn pathology in Parkinson's disease (PD) and alpha-synucleinopathies. Accumulation of phosphorylated alpha-syn fibrils in Lewy bodies and Lewy neurites is the histological hallmark of these diseases. However, it is unclear how phosphorylation relates to alpha-syn pathology. Here, by combining chemical synthesis and bacterial expression, we obtained homogeneous alpha-syn fibrils with site-specific phosphorylation at Y39, which exhibits enhanced neuronal pathology in rat primary cortical neurons. We determined the cryo-electron microscopy (cryo-EM) structure of the pY39 alpha-syn fibril, which reveals a fold of alpha-syn with pY39 in the center of the fibril core forming an electrostatic interaction network with eight charged residues in the N-terminal region of alpha-syn. This structure composed of residues 1 to 100 represents the largest alpha-syn fibril core determined so far. This work provides structural understanding on the pathology of the pY39 alpha-syn fibril and highlights the importance of PTMs in defining the polymorphism and pathology of amyloid fibrils in neurodegenerative diseases. | |||
Parkinson's disease-related phosphorylation at Tyr39 rearranges alpha-synuclein amyloid fibril structure revealed by cryo-EM.,Zhao K, Lim YJ, Liu Z, Long H, Sun Y, Hu JJ, Zhao C, Tao Y, Zhang X, Li D, Li YM, Liu C Proc Natl Acad Sci U S A. 2020 Jul 31. pii: 1922741117. doi:, 10.1073/pnas.1922741117. PMID:32737160<ref>PMID:32737160</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6l1t" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Alpha-synuclein|Alpha-synuclein]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Latest revision as of 13:09, 23 October 2024
Cryo-EM structure of phosphorylated Tyr39 a-synuclein amyloid fibrilCryo-EM structure of phosphorylated Tyr39 a-synuclein amyloid fibril
Structural highlights
Publication Abstract from PubMedPosttranslational modifications (PTMs) of alpha-synuclein (alpha-syn), e.g., phosphorylation, play an important role in modulating alpha-syn pathology in Parkinson's disease (PD) and alpha-synucleinopathies. Accumulation of phosphorylated alpha-syn fibrils in Lewy bodies and Lewy neurites is the histological hallmark of these diseases. However, it is unclear how phosphorylation relates to alpha-syn pathology. Here, by combining chemical synthesis and bacterial expression, we obtained homogeneous alpha-syn fibrils with site-specific phosphorylation at Y39, which exhibits enhanced neuronal pathology in rat primary cortical neurons. We determined the cryo-electron microscopy (cryo-EM) structure of the pY39 alpha-syn fibril, which reveals a fold of alpha-syn with pY39 in the center of the fibril core forming an electrostatic interaction network with eight charged residues in the N-terminal region of alpha-syn. This structure composed of residues 1 to 100 represents the largest alpha-syn fibril core determined so far. This work provides structural understanding on the pathology of the pY39 alpha-syn fibril and highlights the importance of PTMs in defining the polymorphism and pathology of amyloid fibrils in neurodegenerative diseases. Parkinson's disease-related phosphorylation at Tyr39 rearranges alpha-synuclein amyloid fibril structure revealed by cryo-EM.,Zhao K, Lim YJ, Liu Z, Long H, Sun Y, Hu JJ, Zhao C, Tao Y, Zhang X, Li D, Li YM, Liu C Proc Natl Acad Sci U S A. 2020 Jul 31. pii: 1922741117. doi:, 10.1073/pnas.1922741117. PMID:32737160[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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