Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007 Oct 1;63(Pt 10):819-24. Epub 2007 Sep 19.

Structure of Alzheimer's disease amyloid precursor protein copper-binding domain at atomic resolution.

Author information

  • 1Biota Structural Biology Laboratory, St Vincent's Institute, 9 Princes Street, Fitzroy, Victoria 3065, Australia.

Abstract

Amyloid precursor protein (APP) plays a central role in the pathogenesis of Alzheimer's disease, as its cleavage generates the Abeta peptide that is toxic to cells. APP is able to bind Cu2+ and reduce it to Cu+ through its copper-binding domain (CuBD). The interaction between Cu2+ and APP leads to a decrease in Abeta production and to alleviation of the symptoms of the disease in mouse models. Structural studies of CuBD have been undertaken in order to better understand the mechanism behind the process. Here, the crystal structure of CuBD in the metal-free form determined to ultrahigh resolution (0.85 A) is reported. The structure shows that the copper-binding residues of CuBD are rather rigid but that Met170, which is thought to be the electron source for Cu2+ reduction, adopts two different side-chain conformations. These observations shed light on the copper-binding and redox mechanisms of CuBD. The structure of CuBD at atomic resolution provides an accurate framework for structure-based design of molecules that will deplete Abeta production.

PMID:
17909280
[PubMed - indexed for MEDLINE]
PMCID:
PMC2339725
Free PMC Article

Images from this publication.See all images (3)Free text

Figure 1
Figure 2
Figure 3
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for International Union of Crystallography Icon for PubMed Central
    Loading ...
    Write to the Help Desk