Prion Proteins Form Stable Beta-Sheet Structures

Researchers studying how prion particles interact to form long threads of amyloid fibrils have found that in water the mouse PrP106-126 protein fragment assumes a stable structure of parallel beta-sheets that are tightly packed against each other.

Investigators at the Fox Chase Cancer Center (Philadelphia, PA, USA) and at Gifu University (Japan) employed electron microscopy, circular dichroism (CD) spectroscopy, nuclear magnetic resonance (NMR)-detected hydrogen-deuterium exchange measurements, and molecular dynamics simulations to study folding and unfolding of prion proteins. They reported in the December 9, 2003, issue of the Proceedings of the [U.S.] National Academy of Sciences that the fibrils contain approximately 50% beta-sheet structure that in water assumes a stable structure consisting of two four-stranded parallel beta-sheets tightly packed against each other by methyl-methyl interactions.

"Unraveling the molecular basis of this fundamental process is a necessary first step toward treating these diseases,” explained senior author Dr. Heinrich Roder, a biophysicist at Fox Chase Cancer Center. "Unlike other amyloid fibrils, prion particles can interact with the normal host protein and transmit the disease from one individual to another.”

"Understanding the physical principles underlying the folding of proteins is a major challenge of molecular biophysics,” said Dr. Roder. "Because aggregation of misfolded proteins can lead to disease, this basic knowledge has important implications for medicine as well as bioinformatics, biotechnology, and cell biology.”



Related Links:
Fox Chase Cancer Center
Gifu University