Interactions among prions and prion “strains” in yeast

Bradley, Michael E.; Edskes, Herman K.; Hong, Joo Y.; Wickner, Reed B.; Liebman, Susan W.

doi:10.1073/pnas.152330699

Cited by 240 publications

(286 citation statements)

References 59 publications

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“…Although amyloid of Rnq1 153-405 clearly has a parallel inregister ␤-sheet structure, two-dimensional 13 C-13 C NMR experiments show line widths suggestive of significant structural heterogeneity among fibrils, consistent with the known existence of multiple [PIN ϩ ] prion variants (12). Most or all of the variants must share the parallel in-register ␤-sheet structure as a common feature, but the locations of turns or other details may differ among fibrils.…”

Section: Discussionmentioning

confidence: 58%

“…Although Rnq1p and Sup35p form largely separate amyloid aggregates in vivo (10), it is likely that the mechanism of priming of [PSI ϩ ] generation by [PIN ϩ ] is a direct, but rare, addition of Sup35p to the fibrils of Rnq1p (11). Several variants of [PIN ϩ ] are recognized (12,13), distinguished by the efficiency with which they induce the appearance of [PSI ϩ ] and [URE3]. As has been shown for [PSI ϩ ] (14), it is likely that variants of [PIN ϩ ] are different amyloid structures, although the precise nature of such differences remains unknown for any system at present.…”

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confidence: 99%

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Amyloid of Rnq1p, the basis of the [ PIN ⁺ ] prion, has a parallel in-register β-sheet structure

Wickner

Dyda²,

Tycko³

2008

Proc. Natl. Acad. Sci. U.S.A.

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139

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The [PIN ؉ ] prion, a self-propagating amyloid form of Rnq1p, increases the frequency with which the [PSI ؉ ] or [URE3] prions arise de novo. Like the prion domains of Sup35p and Ure2p, Rnq1p is rich in N and Q residues, but rnq1⌬ strains have no known phenotype except for inability to propagate the [PIN ؉ ] prion. We used solidstate NMR methods to examine amyloid formed in vitro from recombinant Rnq1 prion domain (residues 153-405) labeled with Tyr-1-13 C (14 residues), Leu-1-13 C (7 residues), or Ala-3-13 C (13 residues). The carbonyl chemical shifts indicate that most Tyr and Leu residues are in ␤-sheet conformation. Experiments designed to measure the distance from each labeled residue to the next nearest labeled carbonyl showed that almost all Tyr and Leu carbonyl carbon atoms were Ϸ0.5 nm from the next nearest Tyr and Leu residues, respectively. This result indicates that the Rnq1 prion domain forms amyloid consisting of parallel ␤-strands that are either in register or are at most one amino acid out of register. Similar experiments with Ala-3-13 C indicate that the ␤-strands are indeed in-register. The parallel in-register structure, now demonstrated for each of the yeast prions, explains the faithful templating of prion strains, and suggests as well a mechanism for the rare hetero-priming that is [PIN ؉ ]'s defining characteristic.T hree genetic criteria designed to identify infectious proteins [PIN ϩ ] has all of the genetic properties of a prion (4, 5), and was shown to be a self-propagating amyloid form of Rnq1p (4, 6), a protein rich in asparagine (N) and glutamine (Q), which had been shown to form self-propagating aggregates in vivo (7). Deletion of the RNQ1 gene produces no evident phenotype (7) (14), it is likely that variants of [PIN ϩ ] are different amyloid structures, although the precise nature of such differences remains unknown for any system at present.Aggregates formed in vitro from Rnq1p are filamentous and stain with thioflavin T (7). Circular dichroism indicates that these aggregates are high in ␤-sheet content and, on exposure to proteinase K, show partial resistance (6). These studies indicate that the Rnq1p aggregates are amyloid fibers. Moreover, these fibers formed in vitro from recombinant Rnq1p are infectious for yeast spheroplasts, efficiently transmitting the [PIN ϩ ] gene (6).Because amyloid is neither soluble nor crystalline, neither solution NMR nor x-ray crystallography is suitable for elucidating its detailed structure, although the study of amyloid-like microcrystals of short oligopeptides has revealed details of packing and sidechain interactions that are relevant to amyloid structures (15,16). Electron spin resonance studies have been used to study amylin (IAPP) and ␣-synuclein (17, 18) as well as amyloid of PrP (19). Solid-state NMR has been particularly useful for the elucidation of the structure of amyloids (reviewed in ref. 20). Selective labeling of particular amino acid residues with magnetic nuclear isotopes 13 C and 15 N, combined with pulse sequences designed...

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Section: Discussionmentioning

confidence: 58%

mentioning

confidence: 99%

Amyloid of Rnq1p, the basis of the [ PIN ⁺ ] prion, has a parallel in-register β-sheet structure

Wickner

Dyda²,

Tycko³

2008

Proc. Natl. Acad. Sci. U.S.A.

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139

130

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“…Reported antagonistic interactions between prions also suggest a direct interaction (43,44). Indeed, binding of a Q͞N-rich domain to the growth tip of a heterologous prion seed that could occasionally lead to the formation of a novel prion might also block the propagation of the heterologous seed.…”

Section: Discussionmentioning

confidence: 99%

Effects of Q/N-rich, polyQ, and non-polyQ amyloids on thede novoformation of the [PSI⁺] prion in yeast and aggregation of Sup35in vitro

Derkatch

Uptain²,

Outeiro³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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“…In addition to their reactivity with amyloid-specific dyes like ThT, other criteria can be used experimentally to determine whether intracellular aggregates are amyloid-like, such as their unusual resistance to chemical solubilization..The detergent insolubility of amyloids has been used to isolate amyloid-containing fractions from yeast cell lysate by centrifugation (Sondheimer and Lindquist 2000;Bradley et al 2002). In a typical amyloid sedimentation experiment 10 ml of yeast cells are grown to mid-logarithmic phase.…”

Section: Sedimentation Assaymentioning

confidence: 99%

Biochemical, Cell Biological, and Genetic Assays to Analyze Amyloid and Prion Aggregation in Yeast

Alberti

Halfmann

Lindquist

2010

Methods in Enzymology

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Interactions among prions and prion “strains” in yeast

Cited by 240 publications

References 59 publications

Amyloid of Rnq1p, the basis of the [ PIN ⁺ ] prion, has a parallel in-register β-sheet structure

Amyloid of Rnq1p, the basis of the [ PIN ⁺ ] prion, has a parallel in-register β-sheet structure

Effects of Q/N-rich, polyQ, and non-polyQ amyloids on thede novoformation of the [PSI⁺] prion in yeast and aggregation of Sup35in vitro

Biochemical, Cell Biological, and Genetic Assays to Analyze Amyloid and Prion Aggregation in Yeast

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Interactions among prions and prion “strains” in yeast

Cited by 240 publications

References 59 publications

Amyloid of Rnq1p, the basis of the [ PIN + ] prion, has a parallel in-register β-sheet structure

Amyloid of Rnq1p, the basis of the [ PIN + ] prion, has a parallel in-register β-sheet structure

Effects of Q/N-rich, polyQ, and non-polyQ amyloids on thede novoformation of the [PSI+] prion in yeast and aggregation of Sup35in vitro

Biochemical, Cell Biological, and Genetic Assays to Analyze Amyloid and Prion Aggregation in Yeast

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Amyloid of Rnq1p, the basis of the [ PIN ⁺ ] prion, has a parallel in-register β-sheet structure

Amyloid of Rnq1p, the basis of the [ PIN ⁺ ] prion, has a parallel in-register β-sheet structure

Effects of Q/N-rich, polyQ, and non-polyQ amyloids on thede novoformation of the [PSI⁺] prion in yeast and aggregation of Sup35in vitro