Send to

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14126-31. Epub 2002 Oct 21.

Stabilities and conformations of Alzheimer's beta -amyloid peptide oligomers (Abeta 16-22, Abeta 16-35, and Abeta 10-35): Sequence effects.

Author information

  • 1Laboratory of Experimental and Computational Biology, and Intramural Research Support Program, Science Applications International Corporation, National Cancer Institute, Building 469, Room 151, Frederick, MD 21702, USA.


Previously, we have studied the minimal oligomer size of an aggregate amyloid seed and the mechanism of seed growth with a multilayer beta-sheet model. Under high temperature simulation conditions, our approach can test the stability of possible amyloid forms. Here, we report our study of oligomers of Alzheimer's amyloid beta-peptide (Abeta) fragments 16-22, 16-35, and 10-35 (abbreviated Abeta(16-22), Abeta(16-35), and Abeta(10-35), respectively). Our simulations indicate that an antiparallel beta-sheet orientation is the most stable for the Abeta(16-22), in agreement with a solid state NMR-based model [Balbach, J. J., Ishii, Y., Antzutkin, O. N., Leapman, R. D., Rizzo, N. W., et al. (2000) Biochemistry 39, 13748-13759]. A model with twenty-four Abeta(16-22) strands indicates a highly twisted fibril. Whereas the short Abeta(16-22) and Abeta(24-36) may exist in fully extended form, the linear parallel beta-sheets for Abeta(16-35) appear impossible, mainly because of the polar region in the middle of the 16-35 sequence. However, a bent double-layered hairpin-like structure (called hook) with the polar region at the turn forms parallel beta-sheets with higher stability. An intra-strand salt-bridge (D23-K28) stabilizes the bent hairpin-like hook structure. The bent double-beta-sheet model for the Abeta(10-35) similarly offers oligomer stability.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center