The proteins that, when mangled, cause "Mad Cow" and similar diseases also help regulate how yeast cells metabolize metals, biochemists report. Exposure to high levels of metals can coax proteins called prions to adopt an abnormal disease-causing conformation, the researchers found. That could explain why outbreaks of prion diseases have popped up in Iceland, Slovakia, and Colorado--regions with soils high in manganese.
Mad Cow disease in cattle, scrapie in sheep, and Creutzfeldt-Jakob disease in humans are all deadly and transmissible conditions in which the brain degenerates. All seemed to be caused by prion proteins that have changed shape so that enzymes can no longer break them down. This altered conformation is widely thought to be responsible for the diseases, because the tangled and essentially indestructible proteins collect in brain tissue (ScienceNOW, July 29 2004). Studies have shown that some metals bind to prion proteins, leading some scientists to wonder whether metals are involved in the shape shift.
Now, biochemist Gerd Multhaup of the Free University of Berlin and colleagues have shown that prions alter metal metabolism in yeast. As a first step, they took a species of yeast that does not normally make prions and added prions that don't cause disease. Copper levels increased 1.6-fold inside these cells while manganese decreased by half compared to yeast without prion proteins, the researchers report in a paper to be published 13 June in Biochemistry. The researchers then added copper or manganese to the growth medium to form 1 to 5 millimolar concentrations; both additions transformed the prions to the indestructible form.
At one time a skeptic, Multhaup says the new findings and prior evidence are starting to convince him that exposure to metal-enriched food and soils "is a risk factor" that increases susceptibility to prion diseases.
David Brown, a neurochemist at the University of Bath in the United Kingdom, doesn't go that far but says the paper is "a good confirmation" that metals strongly influence prions. And yeast molecular biologist Mick Tuite of the University of Kent in the United Kingdom says that "any attempt to try and model prion conversion in vivo is an important step forward." But he questions the relevance of a yeast species that doesn't usually have prions and says more work in necessary to prove prions behave the same way in mammals.
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