3q9h: Difference between revisions
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==LVFFA segment from Alzheimer's Amyloid-Beta displayed on 42-membered macrocycle scaffold== | |||
<StructureSection load='3q9h' size='340' side='right' caption='[[3q9h]], [[Resolution|resolution]] 2.25Å' scene=''> | |||
{ | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3q9h]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q9H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3Q9H FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BU1:1,4-BUTANEDIOL'>BU1</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | |||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=HAO:{[3-(HYDRAZINOCARBONYL)-4-METHOXYPHENYL]AMINO}(OXO)ACETIC+ACID'>HAO</scene>, <scene name='pdbligand=ORN:L-ORNITHINE'>ORN</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3q9g|3q9g]], [[3q9i|3q9i]], [[3q9j|3q9j]]</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3q9h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q9h OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3q9h RCSB], [http://www.ebi.ac.uk/pdbsum/3q9h PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Protein amyloid oligomers have been strongly linked to amyloid diseases and can be intermediates to amyloid fibers. beta-Sheets have been identified in amyloid oligomers. However, because of their transient and highly polymorphic properties, the details of their self-association remain elusive. Here we explore oligomer structure using a model system: macrocyclic peptides. Key amyloidogenic sequences from Abeta and tau were incorporated into macrocycles, thereby restraining them to beta-strands, but limiting the growth of the oligomers so they may crystallize and cannot fibrillate. We determined the atomic structures for four such oligomers, and all four reveal tetrameric interfaces in which beta-sheet dimers pair together by highly complementary, dry interfaces, analogous to steric zippers found in fibers, suggesting a common structure for amyloid oligomers and fibers. In amyloid fibers, the axes of the paired sheets are either parallel or antiparallel, whereas the oligomeric interfaces display a variety of sheet-to-sheet pairing angles, offering a structural explanation for the heterogeneity of amyloid oligomers. | |||
Characteristics of Amyloid-Related Oligomers Revealed by Crystal Structures of Macrocyclic beta-Sheet Mimics.,Liu C, Sawaya MR, Cheng PN, Zheng J, Nowick JS, Eisenberg D J Am Chem Soc. 2011 May 4;133(17):6736-44. Epub 2011 Apr 7. PMID:21473620<ref>PMID:21473620</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
[[Category: Cheng, P | == References == | ||
[[Category: Eisenberg, D | <references/> | ||
[[Category: Liu, C | __TOC__ | ||
[[Category: Nowick, J S | </StructureSection> | ||
[[Category: Sawaya, M R | [[Category: Cheng, P]] | ||
[[Category: Zheng, J | [[Category: Eisenberg, D]] | ||
[[Category: Liu, C]] | |||
[[Category: Nowick, J S]] | |||
[[Category: Sawaya, M R]] | |||
[[Category: Zheng, J]] | |||
[[Category: Beta sheet tetramer]] | [[Category: Beta sheet tetramer]] | ||
[[Category: Beta-sheet mimetic]] | [[Category: Beta-sheet mimetic]] | ||
[[Category: Macrocyclic peptide]] | [[Category: Macrocyclic peptide]] | ||
[[Category: Protein fibril]] | [[Category: Protein fibril]] | ||
Revision as of 13:21, 19 December 2014
LVFFA segment from Alzheimer's Amyloid-Beta displayed on 42-membered macrocycle scaffoldLVFFA segment from Alzheimer's Amyloid-Beta displayed on 42-membered macrocycle scaffold
Structural highlights
Publication Abstract from PubMedProtein amyloid oligomers have been strongly linked to amyloid diseases and can be intermediates to amyloid fibers. beta-Sheets have been identified in amyloid oligomers. However, because of their transient and highly polymorphic properties, the details of their self-association remain elusive. Here we explore oligomer structure using a model system: macrocyclic peptides. Key amyloidogenic sequences from Abeta and tau were incorporated into macrocycles, thereby restraining them to beta-strands, but limiting the growth of the oligomers so they may crystallize and cannot fibrillate. We determined the atomic structures for four such oligomers, and all four reveal tetrameric interfaces in which beta-sheet dimers pair together by highly complementary, dry interfaces, analogous to steric zippers found in fibers, suggesting a common structure for amyloid oligomers and fibers. In amyloid fibers, the axes of the paired sheets are either parallel or antiparallel, whereas the oligomeric interfaces display a variety of sheet-to-sheet pairing angles, offering a structural explanation for the heterogeneity of amyloid oligomers. Characteristics of Amyloid-Related Oligomers Revealed by Crystal Structures of Macrocyclic beta-Sheet Mimics.,Liu C, Sawaya MR, Cheng PN, Zheng J, Nowick JS, Eisenberg D J Am Chem Soc. 2011 May 4;133(17):6736-44. Epub 2011 Apr 7. PMID:21473620[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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