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| | <StructureSection load='5f1w' size='340' side='right'caption='[[5f1w]], [[Resolution|resolution]] 2.16Å' scene=''> | | <StructureSection load='5f1w' size='340' side='right'caption='[[5f1w]], [[Resolution|resolution]] 2.16Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5f1w]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F1W OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5F1W FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5f1w]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F1W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5F1W FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.161Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=DHI:D-HISTIDINE'>DHI</scene>, <scene name='pdbligand=DLE:D-LEUCINE'>DLE</scene>, <scene name='pdbligand=DSN:D-SERINE'>DSN</scene>, <scene name='pdbligand=DTH:D-THREONINE'>DTH</scene>, <scene name='pdbligand=DVA:D-VALINE'>DVA</scene>, <scene name='pdbligand=IOY:P-IODO-D-PHENYLALANINE'>IOY</scene>, <scene name='pdbligand=MV9:(2~{R})-3-METHYL-2-(METHYLAMINO)BUTANOIC+ACID'>MV9</scene>, <scene name='pdbligand=ORD:D-ORNITHINE'>ORD</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=DHI:D-HISTIDINE'>DHI</scene>, <scene name='pdbligand=DLE:D-LEUCINE'>DLE</scene>, <scene name='pdbligand=DSN:D-SERINE'>DSN</scene>, <scene name='pdbligand=DTH:D-THREONINE'>DTH</scene>, <scene name='pdbligand=DVA:D-VALINE'>DVA</scene>, <scene name='pdbligand=IOY:P-IODO-D-PHENYLALANINE'>IOY</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=MV9:(2~{R})-3-METHYL-2-(METHYLAMINO)BUTANOIC+ACID'>MV9</scene>, <scene name='pdbligand=ORD:D-ORNITHINE'>ORD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5f1t|5f1t]]</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=5f1w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f1w OCA], [https://pdbe.org/5f1w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5f1w RCSB], [https://www.ebi.ac.uk/pdbsum/5f1w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5f1w ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5f1w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f1w OCA], [http://pdbe.org/5f1w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5f1w RCSB], [http://www.ebi.ac.uk/pdbsum/5f1w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5f1w ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Nowick, J S]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Salveson, P J]] | + | [[Category: Nowick JS]] |
| - | [[Category: Spencer, R K]] | + | [[Category: Salveson PJ]] |
| - | [[Category: Beta-hairpin]] | + | [[Category: Spencer RK]] |
| - | [[Category: Immune system]]
| + | |
| Structural highlights
5f1w is a 6 chain structure with sequence from Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.161Å |
| Ligands: | , , , , , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Publication Abstract from PubMed
Oligomeric assemblies of the protein alpha-synuclein are thought to cause neurodegeneration in Parkinson's disease and related synucleinopathies. Characterization of alpha-synuclein oligomers at high resolution is an outstanding challenge in the field of structural biology. The absence of high-resolution structures of oligomers formed by alpha-synuclein impedes understanding the synucleinopathies at the molecular level. This paper reports the X-ray crystallographic structure of oligomers formed by a peptide derived from residues 36-55 of alpha-synuclein. The peptide 1a adopts a beta-hairpin structure, which assembles in a hierarchical fashion. Three beta-hairpins assemble to form a triangular trimer. Three copies of the triangular trimer assemble to form a basket-shaped nonamer. Two nonamers pack to form an octadecamer. Molecular modeling suggests that full-length alpha-synuclein may also be able to assemble in this fashion. Circular dichroism spectroscopy demonstrates that peptide 1a interacts with anionic lipid bilayer membranes, like oligomers of full-length alpha-synuclein. LDH and MTT assays demonstrate that peptide 1a is toxic toward SH-SY5Y cells. Comparison of peptide 1a to homologues suggests that this toxicity results from nonspecific interactions with the cell membrane. The oligomers formed by peptide 1a are fundamentally different than the proposed models of the fibrils formed by alpha-synuclein and suggest that alpha-Syn36-55, rather than the NAC, may nucleate oligomer formation.
X-ray Crystallographic Structure of Oligomers Formed by a Toxic beta-Hairpin Derived from alpha-Synuclein: Trimers and Higher-Order Oligomers.,Salveson PJ, Spencer RK, Nowick JS J Am Chem Soc. 2016 Apr 6;138(13):4458-67. doi: 10.1021/jacs.5b13261. Epub 2016, Mar 23. PMID:26926877[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Salveson PJ, Spencer RK, Nowick JS. X-ray Crystallographic Structure of Oligomers Formed by a Toxic beta-Hairpin Derived from alpha-Synuclein: Trimers and Higher-Order Oligomers. J Am Chem Soc. 2016 Apr 6;138(13):4458-67. doi: 10.1021/jacs.5b13261. Epub 2016, Mar 23. PMID:26926877 doi:http://dx.doi.org/10.1021/jacs.5b13261
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