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-
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Contact: Prof. K. Wuethrich
rr@mol.biol.ethz.ch
+41 (0)1 633 24 73
Swiss National Science Foundation
13-Aug-1997