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High-resolution structure of infectious prion protein: the final frontier

Nature Structural & Molecular Biology volume 19, pages 370–377 (2012)Cite this article

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Abstract

Prions are the proteinaceous infectious agents responsible for the transmission of prion diseases. The main or sole component of prions is the misfolded prion protein (PrPSc), which is able to template the conversion of the host's natively folded form of the protein (PrPC). The detailed mechanism of prion replication and the high-resolution structure of PrPSc are unknown. The currently available information on PrPSc structure comes mostly from low-resolution biophysical techniques, which have resulted in quite divergent models. Recent advances in the production of infectious prions, using very pure recombinant protein, offer new hope for PrPSc structural studies. This review highlights the importance of, challenges for and recent progress toward elucidating the elusive structure of PrPSc, arguably the major pending milestone to reach in understanding prions.

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Figure 1: Potential roles of non-PrP cofactor molecules during conversion of PrPC into PrPSc.
Figure 2: Alternative models proposed for the structure of PrPSc.

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Acknowledgements

We are very grateful to V. Daggett and W. Chen from the University of Washington in Seattle for kindly providing a model for the β-spiral structure of PrPSc. We also want to thank W. Surewicz from Case Western Reserve University for providing high-resolution pictures for the extended in-register β-sheet model and H. Wille from University of California, San Francisco, for providing structural coordinates for the β-helix model. This work was funded in part by US National Institutes of Health grant R01NS041973 to C.S.

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  1. Department of Neurology, Mitchell Center for Alzheimer's Disease and Related Brain Disorders, University of Texas Medical School, Houston, Texas, USA

    Rodrigo Diaz-Espinoza & Claudio Soto

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Correspondence to Claudio Soto.

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Diaz-Espinoza, R., Soto, C. High-resolution structure of infectious prion protein: the final frontier. Nat Struct Mol Biol 19, 370–377 (2012). https://doi.org/10.1038/nsmb.2266

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