Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 133, Issue 17, Pages 6736-6744Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja200222n
Keywords
-
Categories
Funding
- NIH [GM-49076, AG-029430]
- NSF
- HHMI
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [0958111] Funding Source: National Science Foundation
- Direct For Mathematical & Physical Scien
- Division Of Chemistry [0750523] Funding Source: National Science Foundation
Ask authors/readers for more resources
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 A beta 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available