The structural basis of yeast prion strain variants - PubMed (original) (raw)
. 2007 Sep 13;449(7159):233-7.
doi: 10.1038/nature06108. Epub 2007 Sep 2.
Affiliations
- PMID: 17767153
- DOI: 10.1038/nature06108
The structural basis of yeast prion strain variants
Brandon H Toyama et al. Nature. 2007.
Abstract
Among the many surprises to arise from studies of prion biology, perhaps the most unexpected is the strain phenomenon whereby a single protein can misfold into structurally distinct, infectious states that cause distinguishable phenotypes. Similarly, proteins can adopt a spectrum of conformations in non-infectious diseases of protein folding; some are toxic and others are well tolerated. However, our understanding of the structural differences underlying prion strains and how these differences alter their physiological impact remains limited. Here we use a combination of solution NMR, amide hydrogen/deuterium (H/D) exchange and mutagenesis to study the structural differences between two strain conformations, termed Sc4 and Sc37 (ref. 5), of the yeast Sup35 prion. We find that these two strains have an overlapping amyloid core spanning most of the Gln/Asn-rich first 40 amino acids that is highly protected from H/D exchange and very sensitive to mutation. These features indicate that the cores are composed of tightly packed beta-sheets possibly resembling 'steric zipper' structures revealed by X-ray crystallography of Sup35-derived peptides. The stable structure is greatly expanded in the Sc37 conformation to encompass the first 70 amino acids, revealing why this strain shows increased fibre stability and decreased ability to undergo chaperone-mediated replication. Our findings establish that prion strains involve large-scale conformational differences and provide a structural basis for understanding a broad range of functional studies, including how conformational changes alter the physiological impact of prion strains.
Similar articles
- Conformational variations in an infectious protein determine prion strain differences.
Tanaka M, Chien P, Naber N, Cooke R, Weissman JS. Tanaka M, et al. Nature. 2004 Mar 18;428(6980):323-8. doi: 10.1038/nature02392. Nature. 2004. PMID: 15029196 - The physical basis of how prion conformations determine strain phenotypes.
Tanaka M, Collins SR, Toyama BH, Weissman JS. Tanaka M, et al. Nature. 2006 Aug 3;442(7102):585-9. doi: 10.1038/nature04922. Epub 2006 Jun 28. Nature. 2006. PMID: 16810177 - Mechanism of cross-species prion transmission: an infectious conformation compatible with two highly divergent yeast prion proteins.
Tanaka M, Chien P, Yonekura K, Weissman JS. Tanaka M, et al. Cell. 2005 Apr 8;121(1):49-62. doi: 10.1016/j.cell.2005.03.008. Cell. 2005. PMID: 15820678 - [New aspects of research upon the yeast Saccharomyces cerevisiae [PSI+] prion].
Ishikawa T. Ishikawa T. Postepy Biochem. 2007;53(2):182-7. Postepy Biochem. 2007. PMID: 17969880 Review. Polish. - Prions: infectious proteins with genetic properties.
Ter-Avanesyan MD, Kushnirov VV. Ter-Avanesyan MD, et al. Biochemistry (Mosc). 1999 Dec;64(12):1382-90. Biochemistry (Mosc). 1999. PMID: 10648962 Review.
Cited by
- Disruption of the nascent polypeptide-associated complex leads to reduced polyglutamine aggregation and toxicity.
Dublin-Ryan LB, Bhadra AK, True HL. Dublin-Ryan LB, et al. PLoS One. 2024 Aug 15;19(8):e0303008. doi: 10.1371/journal.pone.0303008. eCollection 2024. PLoS One. 2024. PMID: 39146256 Free PMC article. - Multiple aspects of amyloid dynamics in vivo integrate to establish prion variant dominance in yeast.
Norton J, Seah N, Santiago F, Sindi SS, Serio TR. Norton J, et al. Front Mol Neurosci. 2024 Jul 30;17:1439442. doi: 10.3389/fnmol.2024.1439442. eCollection 2024. Front Mol Neurosci. 2024. PMID: 39139213 Free PMC article. - Measuring prion propagation in single bacteria elucidates a mechanism of loss.
Jager K, Orozco-Hidalgo MT, Springstein BL, Joly-Smith E, Papazotos F, McDonough E, Fleming E, McCallum G, Yuan AH, Hilfinger A, Hochschild A, Potvin-Trottier L. Jager K, et al. Proc Natl Acad Sci U S A. 2023 Sep 26;120(39):e2221539120. doi: 10.1073/pnas.2221539120. Epub 2023 Sep 22. Proc Natl Acad Sci U S A. 2023. PMID: 37738299 Free PMC article. - Overexpression of Hsp104 by Causing Dissolution of the Prion Seeds Cures the Yeast [PSI+] Prion.
Stanford KE, Zhao X, Kim N, Masison DC, Greene LE. Stanford KE, et al. Int J Mol Sci. 2023 Jun 29;24(13):10833. doi: 10.3390/ijms241310833. Int J Mol Sci. 2023. PMID: 37446010 Free PMC article. - Amino acid homorepeats in proteins.
Chavali S, Singh AK, Santhanam B, Babu MM. Chavali S, et al. Nat Rev Chem. 2020 Aug;4(8):420-434. doi: 10.1038/s41570-020-0204-1. Epub 2020 Jul 21. Nat Rev Chem. 2020. PMID: 37127972 Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases