Relationship between the cytosolic proteins abundance and their intrinsic properties.

<p>A) Amino acid abundance in high-abundant (pale grey) and low-abundant (dark grey) sequences relative to the expected frequencies in natural proteins as deduced from Swiss-Prot <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009383#pone.0009383-Boeckmann1" target="_blank">[82]</a>. B) Comparison between the proteins pI and Na4vSS values. C) Correlation between proteins hydropathicity (GRAVY) and Na4vSS values.</p

Comparison between cytosolic proteins theoretical expression levels and their aggregation parameters.

<p>A) Cumulative distributions of Na4vSS values in the 10% cytosolic proteins with the highest (black) and lowest (grey) Codon Adaptation Index (CAI) values. B) Correlation between the CAI and the Na4vSS values. Each point represents the average value over all the sequences having a CAI value comprised in an interval of 0.03.</p

Dependence of proteins length on their aggregation properties and chaperone binding affinity.

<p>A) Dot plot distribution represents the relationship between the molecular weight and Na4vSS. Columns show the size distribution of polypeptides that bind to GroEL (grey) or DnaK (white) in <i>E. coli</i> according to the data in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009383#pone.0009383-Ellis1" target="_blank">[61]</a>. B) Relationship between the molecular weight and the NnHS. Each point corresponds to the average value over all the sequences having a length comprised in an interval of 1.9 kDa.</p

Disordered sequence stretches display reduced protein aggregation.

<p>Cumulative distributions of NnHS and Na4vSS values in ribosomal proteins (A and B), intrinsically unstructured proteins (C and D) and disordered fragments in cytosolic proteins (E and F) are compared with the distribution in the complete cytosolic set (grey).</p

Amino acid composition of cytosolic proteins hot spots and their flanks.

<p>A) Amino acid frequencies relative to their average frequency in natural proteins as deduced from Swiss-Prot <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009383#pone.0009383-Boeckmann1" target="_blank">[82]</a>. A relative frequency of 0 for a given residue at a given position means that the residue occupies that position with a frequency identical to that in natural proteins. Residues enrichment in the hot spots (B) and at the flanks (C) relative to their frequency in natural proteins. Values above or below 1.0 point denote increases or decreases in frequency, respectively.</p

The inner membrane contains proteins with different number of transmembrane segments and associated aggregation propensities.

<p>Diagram of the inner membrane protein set showing the Na4vSS value and the number of transmembrane segments.</p

Inner membrane proteins with differential aggregation propensities are involved in different biological functions.

<p>Percentage of inner membrane proteins associated with the biological functions described in FunCat (A) and UniProtKB (B). The inner membrane proteins were divided in two groups according to their Na4vSS value: Na4vSS <6 (42 proteins; pale grey) or Na4vSS ≥6 (43 proteins; dark grey).</p

Different operons regulate proteins with different aggregation propensity and biological function.

<p><i>a Operons regulating proteins with aggregation propensity lower (LA) than the mean aggregation propensity of the complete operon protein set (−6.4 Na4vSS).</i></p><p><i>b Operons regulating proteins with aggregation propensity higher (HA) than the mean aggregation propensity of the complete operon protein set (−6.4 Na4vSS).</i></p

Proteins encoded by the same operon display related aggregation propensities.

<p>Standard deviation of Na4vSS values in the 25 analysed operons. The standard deviation in the complete cytosolic set is 7.72 (dashed line). Low standard deviation within an operon indicates that the aggregation propensity of its proteins is similar.</p

Table_5_Discovering Putative Prion-Like Proteins in Plasmodium falciparum: A Computational and Experimental Analysis.pdf

<p>Prions are a singular subset of proteins able to switch between a soluble conformation and a self-perpetuating amyloid state. Traditionally associated with neurodegenerative diseases, increasing evidence indicates that organisms exploit prion-like mechanisms for beneficial purposes. The ability to transit between conformations is encoded in the so-called prion domains, long disordered regions usually enriched in glutamine/asparagine residues. Interestingly, Plasmodium falciparum, the parasite that causes the most virulent form of malaria, is exceptionally rich in proteins bearing long Q/N-rich sequence stretches, accounting for roughly 30% of the proteome. This biased composition suggests that these protein regions might correspond to prion-like domains (PrLDs) and potentially form amyloid assemblies. To investigate this possibility, we performed a stringent computational survey for Q/N-rich PrLDs on P. falciparum. Our data indicate that ∼10% of P. falciparum protein sequences have prionic signatures, and that this subproteome is enriched in regulatory proteins, such as transcription factors and RNA-binding proteins. Furthermore, we experimentally demonstrate for several of the identified PrLDs that, despite their disordered nature, they contain inner short sequences able to spontaneously self-assemble into amyloid-like structures. Although the ability of these sequences to nucleate the conformational conversion of the respective full-length proteins should still be demonstrated, our analysis suggests that, as previously described for other organisms, prion-like proteins might also play a functional role in P. falciparum.</p