Progress In Prion Research: Three-Dimensional Structure Of Prion Protein Fully Uncovered
A team of researchers from the Institute for Molecular Biology and Biophysics at the Swiss Federal Institute of Technology in Zurich are the first to successfully decode the three-dimensional structure of an intact prion protein.
In their malformed variant, prions appear to induce human Creutzfeld-Jacob disease, and BSE, "mad cow" disease. The research team is supported by the Swiss National Science Foundation. Their work attracted attention a year ago when they published a first part of the structure. The research results to be published on Thursday in the review FEBS Letters indicate that the newly decoded part of the protein structure might play an important role in the conversion of the normal prion protein into its disease-inducing variant.
Prion proteins are chains of proteins normally present in the bodies of humans and animals. They cause disease only when they are folded in a particular way-luckily a very rare occurrence so far. The disease-inducing prions appear to contain clumps of several prion protein molecules, which damage the brain of affected humans or animals. Where and how the clumping occurs has not thus far been clear. Professors Kurt Wuethrich and Rudi Glockshuber, and their research team from the Institute for Molecular Biology and Biophysics at the Swiss Federal Institute of Technology in Zurich have made a further, major contribution to this question. They are the first to fully uncover the complete, three-dimensional structure of the normal prion protein.
Compared with its normal form, prion protein isolated from the brains of cows afflicted with BSE has a higher proportion of so-called beta-sheet-containing folds. This is where clumping may occur in the prion protein. Their studies have led the research team in Zurich to the discovery of a part in the molecule which consists of 98 amino acid residues. In the normal prion protein this part is mobile and attached like a flexible tail to the structure described a year ago, the so-called C-terminal domain PrP (121-231). In protein material from animals afflicted with scrapie or BSE a large part of this "tail" of amino acids is not mobile but part of the rigid molecule structure. According to Wuethrich and Glockshuber, these "results indicate that the conversion of the normal to the disease-inducing form of the prion protein may occur much more easily than has been assumed so far, by way of a new fold in the flexible part of the normal protein."
The publication a year ago of the three-dimensional structure of the C-terminal domain PrP (121-231) of the normal prion protein caused a great stir among the public and the experts. The results being published now both confirm and go beyond those findings. They demonstrate that the structure described then is indeed part of the whole protein. What is new is the discovery that the entire remainder of the molecule is not folded, and highly flexible. Both results are a further step towards a deeper understanding of prion diseases. They will be useful in planning future biochemical and biomedical studies.
rating: 4.00 from 1 votes | updated on: 14 Mar 2010 | views: 3729 |