A Promiscuous Prion: Efficient Induction of [URE3] Prion Formation by Heterologous Prion Domains

The [URE3] and [PSI+] prions are the infections amyloid forms of the Saccharomyces cerevisiae proteins Ure2p and Sup35p, respectively. Randomizing the order of the amino acids in the Ure2 and Sup35 prion domains while retaining amino acid composition does not block prion formation, indicating that amino acid composition, not primary sequence, is the predominant feature driving [URE3] and [PSI+] formation. Here we show that Ure2p promiscuously interacts with various compositionally similar proteins to influence [URE3] levels. Overexpression of scrambled Ure2p prion domains efficiently increases de novo formation of wild-type [URE3] in vivo. In vitro, amyloid aggregates of the scrambled prion domains efficiently seed wild-type Ure2p amyloid formation, suggesting that the wild-type and scrambled prion domains can directly interact to seed prion formation. To test whether interactions between Ure2p and naturally occurring yeast proteins could similarly affect [URE3] formation, we identified yeast proteins with domains that are compositionally similar to the Ure2p prion domain. Remarkably, all but one of these domains were also able to efficiently increase [URE3] formation. These results suggest that a wide variety of proteins could potentially affect [URE3] formation.

Download Full-text

Predicting Interactions Between Pathogen and Human Proteins Based on the Relation Between Sequence Length and Amino Acid Composition

Current Bioinformatics ◽

10.2174/1574893616666210430133846 ◽

2021 ◽

Vol 16 ◽

Author(s):

Saud Alguwaizani ◽

Shulei Ren ◽

De-Shuang Huang ◽

Kyungsook Han

Keyword(s):

Amino Acid ◽

Amino Acid Composition ◽

Yersinia Pestis ◽

Acid Composition ◽

Sequence Length ◽

Support Vector ◽

Human Ppis ◽

Svm Model

Aim: Both bacterial infection and viral infection involve a large number of protein-protein interactions (PPIs) between a pathogen and its target host. Background: So far, many computational methods have focused on predicting PPIs within the same species rather than PPIs across different species. Methods: From the extensive analysis of PPIs between Yersinia pestis bacteria and humans, we recently discovered an interesting relation; a linear relation between amino acid composition and sequence length was observed in many proteins involved in PPIs. We have built a support vector machine (SVM) model, which predicts PPIs between human and bacteria using two feature types derived from the relation. The two feature types used in the SVM are the amino acid composition group (AACG) and the difference in amino acid composition between host and pathogen proteins. Result: The SVM model achieved high performance in predicting bacteria-human PPIs. The model showed an accuracy of 96%, sensitivity of 94%, and specificity of 98% in predicting PPIs between humans and Yersinia pestis, in which there is a strong relation between amino acid composition and sequence length. The SVM model was also tested in predicting PPIs between human and viruses, which include Ebola, HCV, and SARSCoV-2, and showed a good performance. Conclusion: The feature types identified in our study are simple yet powerful in predicting pathogen-human PPIs. Although preliminary, our method will be useful for finding unknown target host proteins or pathogen proteins and designing in vitro or in vivo experiments.

Download Full-text

Scrambled Prion Domains Form Prions and Amyloid

Molecular and Cellular Biology ◽

10.1128/mcb.24.16.7206-7213.2004 ◽

2004 ◽

Vol 24 (16) ◽

pp. 7206-7213 ◽

Cited By ~ 129

Author(s):

Eric D. Ross ◽

Ulrich Baxa ◽

Reed B. Wickner

Keyword(s):

Amino Acid ◽

Amino Acid Composition ◽

Acid Composition ◽

Sequence Composition ◽

Amino Terminal ◽

Rich Domain ◽

The Many ◽

Necessary And Sufficient

ABSTRACT The [URE3] prion of Saccharomyces cerevisiae is a self-propagating amyloid form of Ure2p. The amino-terminal prion domain of Ure2p is necessary and sufficient for prion formation and has a high glutamine (Q) and asparagine (N) content. Such Q/N-rich domains are found in two other yeast prion proteins, Sup35p and Rnq1p, although none of the many other yeast Q/N-rich domain proteins have yet been found to be prions. To examine the role of amino acid sequence composition in prion formation, we used Ure2p as a model system and generated five Ure2p variants in which the order of the amino acids in the prion domain was randomly shuffled while keeping the amino acid composition and C-terminal domain unchanged. Surprisingly, all five formed prions in vivo, with a range of frequencies and stabilities, and the prion domains of all five readily formed amyloid fibers in vitro. Although it is unclear whether other amyloid-forming proteins would be equally resistant to scrambling, this result demonstrates that [URE3] formation is driven primarily by amino acid composition, largely independent of primary sequence.

Download Full-text

Effects of autoclaving and sodium diformate supplementation to diets on amino acid composition, in vivo digestibility in mink (Neovison vison) and in vitro bioavailability using digestive enzymes from Atlantic salmon (Salmo salar)

Animal Feed Science and Technology ◽

10.1016/j.anifeedsci.2012.09.010 ◽

2012 ◽

Vol 178 (1-2) ◽

pp. 84-94 ◽

Cited By ~ 6

Author(s):

Thea Morken ◽

Francisco Javier Moyano ◽

Lorenzo Márquez ◽

Mette Sørensen ◽

Liv Torunn Mydland ◽

...

Keyword(s):

Amino Acid ◽

Atlantic Salmon ◽

Amino Acid Composition ◽

Acid Composition ◽

Salmo Salar ◽

Digestive Enzymes ◽

Neovison Vison ◽

Atlantic Salmon Salmo Salar

Download Full-text

Compositional Determinants of Prion Formation in Yeast

Molecular and Cellular Biology ◽

10.1128/mcb.01140-09 ◽

2009 ◽

Vol 30 (1) ◽

pp. 319-332 ◽

Cited By ~ 113

Author(s):

James A. Toombs ◽

Blake R. McCarty ◽

Eric D. Ross

Keyword(s):

Amino Acid ◽

Amino Acid Composition ◽

Amyloid Formation ◽

Yeast Prion ◽

Hydrophobic Residues ◽

Predictive Methods ◽

Infectious Proteins ◽

Β Sheet ◽

Eukaryotic Genomes

ABSTRACT Numerous prions (infectious proteins) have been identified in yeast that result from the conversion of soluble proteins into β-sheet-rich amyloid-like protein aggregates. Yeast prion formation is driven primarily by amino acid composition. However, yeast prion domains are generally lacking in the bulky hydrophobic residues most strongly associated with amyloid formation and are instead enriched in glutamines and asparagines. Glutamine/asparagine-rich domains are thought to be involved in both disease-related and beneficial amyloid formation. These domains are overrepresented in eukaryotic genomes, but predictive methods have not yet been developed to efficiently distinguish between prion and nonprion glutamine/asparagine-rich domains. We have developed a novel in vivo assay to quantitatively assess how composition affects prion formation. Using our results, we have defined the compositional features that promote prion formation, allowing us to accurately distinguish between glutamine/asparagine-rich domains that can form prion-like aggregates and those that cannot. Additionally, our results explain why traditional amyloid prediction algorithms fail to accurately predict amyloid formation by the glutamine/asparagine-rich yeast prion domains.

Download Full-text

Biochemical and genetic characterization of a yeast TFIID mutant that alters transcription in vivo and DNA binding in vitro

Molecular and Cellular Biology ◽

10.1128/mcb.12.5.2372-2382.1992 ◽

1992 ◽

Vol 12 (5) ◽

pp. 2372-2382

Author(s):

K M Arndt ◽

S L Ricupero ◽

D M Eisenmann ◽

F Winston

Keyword(s):

Amino Acid ◽

Dna Binding ◽

Direct Repeat ◽

Single Amino Acid ◽

Wild Type ◽

Dna Binding Specificity ◽

Selection For

A mutation in the gene that encodes Saccharomyces cerevisiae TFIID (SPT15), which was isolated in a selection for mutations that alter transcription in vivo, changes a single amino acid in a highly conserved region of the second direct repeat in TFIID. Among eight independent spt15 mutations, seven cause this same amino acid change, Leu-205 to Phe. The mutant TFIID protein (L205F) binds with greater affinity than that of wild-type TFIID to at least two nonconsensus TATA sites in vitro, showing that the mutant protein has altered DNA binding specificity. Site-directed mutations that change Leu-205 to five different amino acids cause five different phenotypes, demonstrating the importance of this amino acid in vivo. Virtually identical phenotypes were observed when the same amino acid changes were made at the analogous position, Leu-114, in the first repeat of TFIID. Analysis of these mutations and additional mutations in the most conserved regions of the repeats, in conjunction with our DNA binding results, suggests that these regions of the repeats play equivalent roles in TFIID function, possibly in TATA box recognition.

Download Full-text

Amino acid composition and in vitro antioxidant and cytoprotective activity of abalone viscera hydrolysate

Journal of Functional Foods ◽

10.1016/j.jff.2015.04.023 ◽

2015 ◽

Vol 16 ◽

pp. 94-103 ◽

Cited By ~ 31

Author(s):

Jae-Young Je ◽

Soo Yeon Park ◽

Joung-Youl Hwang ◽

Chang-Bum Ahn

Keyword(s):

Amino Acid ◽

Amino Acid Composition ◽

Acid Composition ◽

Cytoprotective Activity

Download Full-text

Novel Salmonella enterica Serovar Typhimurium Protein That Is Indispensable for Virulence and Intracellular Replication

Infection and Immunity ◽

10.1128/iai.69.12.7413-7418.2001 ◽

2001 ◽

Vol 69 (12) ◽

pp. 7413-7418 ◽

Cited By ~ 11

Author(s):

Tahar van der Straaten ◽

Angela van Diepen ◽

Kitty Kwappenberg ◽

Sjaak van Voorden ◽

Kees Franken ◽

...

Keyword(s):

Amino Acid ◽

Protein Function ◽

Salmonella Enterica ◽

Host Cells ◽

Wild Type ◽

Intracellular Replication ◽

Oxygen Intermediates ◽

Serovar Typhimurium

ABSTRACT Upon contact with host cells, the intracellular pathogenSalmonella enterica serovar Typhimurium promotes its uptake, targeting, and survival in intracellular niches. In this process, the bacterium evades the microbicidal effector mechanisms of the macrophage, including oxygen intermediates. This study reports the phenotypic and genotypic characterization of an S. enterica serovar Typhimurium mutant that is hypersusceptible to superoxide. The susceptible phenotype is due to a MudJ insertion-inactivation of a previously undescribedSalmonella gene designated sspJ that is located between 54.4 and 64 min of the Salmonellachromosome and encodes a 392-amino-acid protein. In vivo, upon intraperitoneal injection of 104 to 107bacteria in C3H/HeN and 101 to 104 bacteria in BALB/c mice, the mutant strain was less virulent than the wild type. Consistent with this finding, during the first hour after ingestion by macrophage-like J774 and RAW264.7 cells in vitro, the intracellular killing of the strain carrying sspJ::MudJ is enhanced fivefold over that of wild-type microorganisms. Wild-type salmonellae displayed significant intracellular replication during the first 24 h after uptake, but sspJ::MudJ mutants failed to do so. This phenotype could be restored to that of the wild type by sspJ complementation. The SspJ protein is found in the cytoplasmic membrane and periplasmic space. Amino acid sequence homology analysis did reveal a leader sequence and putative pyrroloquinoline quinone-binding domains, but no putative protein function. We excluded the possibility that SspJ is a scavenger of superoxide or has superoxide dismutase activity.

Download Full-text