Yeast Prion Protein Structure Revealed

Prion proteins are linked to several diseases, including bovine spongiform encephalopathy in cattle, scrapie in sheep, and Creutzfeldt-Jakob disease in humans. Infectious prion-like proteins that also form amyloid fibrils are found in yeast and other fungi. Based on solid-state nuclear magnetic resonance data, Wasmer et al. provide a structural model of amyloid fibrils from the prion-forming domain of the fungal HET-s protein. An earlier preliminary model gave no information on intermolecular B-sheet propagation. The current model shows that the amyloid fibrils form a left-handed B-solenoid with two windings per molecule that is stabilized by hydrophobic and polar interactions and salt bridges.


Sources:

Amyloid Fibrils of the HET-s(218–289) Prion Form a β Solenoid with a Triangular Hydrophobic Core. Wasmer et al. Science 14 March 2008: Vol. 319. no. 5869, pp. 1523 - 1526.

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Mutations associated with Autism

Although autism is highly heritable, sorting out the genes associated with this complex disease has been difficult. Weiss et al. searched for structural mutations (duplications or deletions below the level of microscopic detection) in the genomic DNA of 751 families who are part of the Autism Genetic Resource Exchange. They found a significant association of autism with a nearly 600-kb region that was deleted or duplicated at a locus on chromosome 16. This structural mutation was also observed in patients from Children's Hospital in Boston and in a group from Iceland. It occurred at a frequency of approximately 1% in patients as compared with less than 0.1% of the general population. It might result from unequal crossing over at this region of chromosome 16, which is a known hotspot for deletion and duplication and is bordered by two duplicated regions. Autism may represent the summation of a series of rare events, whose detection will require screening tens of thousands of patient samples.

Sources:

Association between Microdeletion and Microduplication at 16p11.2 and Autism. Weiss et al. N. Engl. J. Med. 358, 667 (2008).

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