About MDD - Subscription Info

October 2000
Vol. 3, No. 8, p. 18.

department/feature icon

Mad protein structures

...Bovine spongiform encephalopathy (BSE), or mad cow disease, is one of a group of fatal neurodegenerative illnesses known as prion diseases. They are thought to be caused by the refolding of a ubiquitous cellular form of the prion protein (PrP) into a disease-related form that aggregates in the brain. Although BSE only affects cattle, there are concerns that it could be transmitted to humans and form a variant of Creutzfeldt–Jakob disease.

Although it is possible to transmit prion diseases within a species, infection between species appears less likely. While PrPs have similar global folds, which are characterized by an unstructured 100-residue tail attached to a similarly sized globular domain, local structural variability may determine this “species barrier”. This question is the focus of two publications from researchers at the Swiss Federal Institute of Technology (Zurich) (Proc. Natl. Acad. Sci. 2000, 97, 8334–8339 and 8340–8345).

Kurt Wuttrich and colleagues determined the structure of the bovine PrP (bPrP) by NMR and compared it with those previously elucidated for mice, Syrian hamsters, and humans. The bPrP structure shows local structural differences that distinguish it from rodent PrP, but it appears to be essentially identical to human PrP. However, bovine and human PrPs differ in the surface distribution of electrostatic charges, which the researchers suggest may be the “principal structural feature of the ‘healthy’ PrP form that might affect the stringency of the species barrier.”

The researchers also determined the NMR structures of three single-residue variants of human PrP. These substitutions correspond to the rodent PrPs in regions showing high species variability. The research shows that single-residue changes in certain areas of the protein have significant effects on overall structure, even though the region in which the change occurs is poorly ordered.

Together, the two studies suggest that the species barriers that we have come to rely on may be only as secure as the surface potential of a single protein.

LEELA HOLLIMAN

Return to Top || Table of Contents