Send to

Choose Destination
See comment in PubMed Commons below
Acc Chem Res. 2004 Jun;37(6):357-64.

Rapid photochemical cross-linking--a new tool for studies of metastable, amyloidogenic protein assemblies.

Author information

Center for Neurologic Diseases, Brigham and Women's Hospital and Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.


Amyloidoses comprise a class of diseases characterized pathologically by the presence of deposits of fibrillar, aberrantly folded proteins, known as amyloids. Historically, these deposits were considered the key factors causing disease. However, recent evidence suggests that soluble protein oligomers, which are precursors for amyloid fibrils, are the primary toxic effectors responsible for the disease process. Understanding the mechanism by which these oligomers exert their toxicity requires knowledge of the structure, kinetics, and thermodynamics of their formation and conversion into larger assemblies. Such studies have been difficult due to the metastable nature of the oligomers. For the amyloid beta-protein (Abeta), a consensus about the size and relative abundance of small oligomers has not been achieved. We describe here the application of the method Photoinduced Cross-Linking of Unmodified Proteins (PICUP) to the study of Abeta oligomerization. This approach distinguishes oligomerization patterns of amyloidogenic and nonamyloidogenic proteins, allows quantification of each component in oligomer mixtures, and provides a means of correlating primary structure modifications with assembly characteristics. PICUP thus is a powerful tool for the investigation of small, metastable protein oligomers. The method provides essential insights into the factors that control the assembly of pathogenic protein oligomers, facilitating efforts toward the development of therapeutic agents.

[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for American Chemical Society Icon for eScholarship, California Digital Library, University of California
    Loading ...
    Support Center