3Q9H: Lvffa Segment From Alzheimer's Amyloid-Beta Displayed On 42-Membered Macrocycle Scaffold

Citation:
Abstract
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.
PDB ID: 3Q9HDownload
MMDB ID: 91220
PDB Deposition Date: 2011/1/7
Updated in MMDB: 2011/06
Experimental Method:
x-ray diffraction
Resolution: 2.25  Å
Source Organism:
Similar Structures:
Biological Unit for 3Q9H: tetrameric; determined by author
Molecular Components in 3Q9H
Label Count Molecule
Proteins (4 molecules)
4
Cyclic Pseudo-peptide Lvffa(orn)(hao)lk(orn)
Molecule annotation
Chemicals (7 molecules)
1
1
2
4
3
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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