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Origins and kinetic consequences of diversity in Sup35 yeast prion fibers

Nature Structural Biology volume 9, pages 389–396 (2002)Cite this article

Abstract

A remarkable feature of prions is that infectious particles composed of the same prion protein can give rise to different phenotypes. This strain phenomenon suggests that a single prion protein can adopt multiple infectious conformations. Here we use a novel single fiber growth assay to examine the heterogeneity of amyloid fibers formed by the yeast Sup35 prion protein. Sup35 spontaneously forms multiple, distinct and faithfully propagating fiber types, which differ dramatically both in their degrees of polarity and overall growth rates. Both in terms of the number of distinct self-propagating fiber types, as well as the ability of these differences to dictate the rate of prion growth, this diversity is well suited to account for the range of prion strain phenotypes observed in vivo.

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Figure 1: NM–HA3 and NM–HA*3 are equivalent except in their affinity for HA antibody.
Figure 2: Visualization of growth from single Sup35-NM fibers.
Figure 3: Sup35-NM fibers have intrinsic differences in their polarities.
Figure 4: At least four subpopulations of Sup35-NM fibers exist.
Figure 5: Elongation rate and polarity are faithfully transmitted by individual Sup35-NM fibers.

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Acknowledgements

We thank S. Rogers and R. Vale for instruction and use of their AFM. We also would like to thank R.D. Mullins, E. O'Shea, W. Lim, P. Chien and V. Denic, as well as the Weissman lab members, for helpful discussion and critical reading of the manuscript. This work was supported by the Howard Hughes Medical Institute, a Howard Hughes Medical Institute predoctoral fellowship (A.H.D.), the David and Lucile Packard Foundation and the National Institutes of Health.

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  1. Howard Hughes Medical Institute and Departments of Cellular & Molecular Pharmacology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, 94143-0450, California, USA

    Angela H. DePace & Jonathan S. Weissman

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Correspondence to Jonathan S. Weissman.

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DePace, A., Weissman, J. Origins and kinetic consequences of diversity in Sup35 yeast prion fibers. Nat Struct Mol Biol 9, 389–396 (2002). https://doi.org/10.1038/nsb786

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