Domain organization and structure-function relationship of the HET-s prion protein of Podospora anserina

Balguerie, Axelle

doi:10.1093/emboj/cdg213

Cited by 201 publications

(284 citation statements)

References 35 publications

(52 reference statements)

Supporting

Mentioning

260

Contrasting

Unclassified

Order By: Relevance

“…This observation does not dismiss the fact that IBs might indeed have an amyloid structure, because even amyloids do not incorporate their entire polypeptide length into the highly packed b-sheet structure as seen in yeast prions (Morgan et al, 2008). The secondary structure content analysis of IBs confirmed that there are fibrillar and nonfibrillar regions included (Balguerie et al, 2003). Moreover comparison of IB formation with an amyloid b-formation revealed a common formation mechanism: primary establishment of an inter-backbone, hydrogen-bonded network that stabilizes b-sheet-rich fibrillar structures and drives the aggregation force.…”

Section: Protein Homeostasis and Bacterial Cellular Responses To Aggrmentioning

confidence: 97%

Protein aggregation in bacteria: the thin boundary between functionality and toxicity

et al. 2013

View full text Add to dashboard Cite

Section: Protein Homeostasis and Bacterial Cellular Responses To Aggrmentioning

confidence: 97%

Protein aggregation in bacteria: the thin boundary between functionality and toxicity

et al. 2013

View full text Add to dashboard Cite

“…1). The Het-s protein lacks the Asn/Gln-rich region characteristic of the yeast prions identified so far, although it is similarly divided into a globular functional region and a flexible prion domain [22]. The relationship between domain structure and function for the PrP protein is more complex.…”

Section: Overviewmentioning

confidence: 99%

“…The Ure2 system is therefore a useful model not only to investigate the prion concept, but also to understand the properties of Gln/ Asn-repeat proteins and hence the molecular basis of the related diseases. [27,29,58], Sup35 [114,115], Rnq1 [13], Het-s [22] and PrP [23,24,116,117]. The functional regions are as indicated.…”

Section: Introductionmentioning

confidence: 99%

The yeast prion protein Ure2: Structure, function and folding

Lian

Jiang

Zhang

et al. 2006

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

View full text Add to dashboard Cite

The Saccharomyces cerevisiae protein Ure2 functions as a regulator of nitrogen metabolism and as a glutathione-dependent peroxidase. Ure2 also has the characteristics of a prion, in that it can undergo a heritable conformational change to an aggregated state; the prion form of Ure2 loses the regulatory function, but the enzymatic function appears to be maintained. A number of factors are found to affect the prion properties of Ure2, including mutation and expression levels of molecular chaperones, and the effect of these factors on structure and stability are being investigated. The relationship between structure, function and folding for the yeast prion Ure2 are discussed.

show abstract

“…The missing resonances of the remaining residues are probably a consequence of dynamical or structural heterogeneity 19 . Deviations of the combined 13 Cα/ 13 Cβ chemical shifts from random coil values were used to identify the type of secondary structure present in HET-s(218-289) fibrils. Negative deviations (Fig.…”

mentioning

confidence: 99%

Correlation of structural elements and infectivity of the HET-s prion

Ritter¹,

Maddelein²,

Siemer³

et al. 2005

Nature

431

485

View full text Add to dashboard Cite

Prions are believed to be infectious self-propagating polymers of otherwise soluble host-encoded proteins 1,2 . This concept is now strongly supported by the recent findings that amyloid fibrils of recombinant prion proteins from yeast 3-5 , Podospora anserina 6 , and mammals 7 can induce prion phenotypes in the corresponding hosts. However, the structural basis of prion infectivity remains largely elusive because acquisition of atomic resolution structural properties of amyloid fibrils represents a largely unsolved technical challenge. HET-s, the prion protein of P. anserina, contains a C-terminal prion domain comprising residues 218-289. Amyloid fibrils of are necessary and sufficient for the induction and propagation of prion infectivity 6 . Here, we have used fluorescence studies, quenched hydrogen exchange NMR and solid state NMR to determine the sequence specific positions of secondary structure elements of amyloid fibrils of . This revealed four β-strands constituted by two pseudo repeat sequences, each forming a β-strandturn-β-strand motif. We show that this conformation is the functional and infectious entity of the HET-s prion by using a structure-based mutagenesis approach. These results correlate for the first time distinct structural elements with prion infectivity.The prion form of the protein HET-s is involved in a programmed cell death phenomenon termed heterokaryon incompatibility 8,9 . This reaction occurs in filamentous fungi when cells of incompatible genotype fuse and form a mixed cell. In P. anserina, two incompatible genotypes, called het-s and het-S, encode for the proteins HET-s and HET-S. They are both 289 amino acids long and differ in only 13 residues 10 . However, only HET-s can form a prion 11 : P. anserina cells expressing the HET-s protein exist either in a prion state called [Hets] Correspondence and requests for materials should be addressed to R.R. (e-mail: riek@salk.edu).. $ these authors contributed equally to this work.Supplementary Information accompanies the paper on Nature's website (http://www.nature.com). (Fig. 1a) contained one assigned cross-peak for each backbone amide of with the exception of 289, enabling a residuespecific determination of the hydrogen exchange rates. Upon exchange in D 2 O buffer for 6 weeks the intensity of about 45% of the resonances was significantly reduced or absent from the spectrum (Fig. 1b). This suggested that the corresponding amides have undergone exchange with solvent deuterons, which are not visible in this experiment. NIH Public AccessThe hydrogen exchange was followed over a total period of 3 months. All residues displayed a mono-exponential decay (Fig. S1) indicating that the structure of the fibrils was well defined and homogeneous. The summarized hydrogen exchange data (Fig. 1e) show that due to exchange rates faster than 5·h -1 , the 8 N-terminal residues, the 5 C-terminal residues and residues 247-261 are only weakly or not protected and may therefore be conformationally disordered. Four segments were observed that d...

show abstract

Domain organization and structure-function relationship of the HET-s prion protein of Podospora anserina

Cited by 201 publications

References 35 publications

Protein aggregation in bacteria: the thin boundary between functionality and toxicity

Protein aggregation in bacteria: the thin boundary between functionality and toxicity

The yeast prion protein Ure2: Structure, function and folding

Correlation of structural elements and infectivity of the HET-s prion

Contact Info

Product

Resources

About