Disorder profile of the cytoplasmic parts of 263 single-pass transmembrane proteins with long cytoplasmic tails.

<p>(>150 residues). Standard errors of the mean values are displayed in yellow.</p

Conserved motif density in long (>150 residues) cytoplasmic tails of single-pass transmembrane.

<p>Conserved motifs density is defined as the number of conserved motifs that span a residue divided by the number of residues that are disordered.</p

Disorder profile of single-pass proteins.

<p>Mean IUPred disorder profile (in red) for residues from 803 human single-pass transmembrane proteins, with respect to distance from the membrane (position 0; extracellular negative, intracellular positive). The membrane region was included in the analysis, but has been omitted from the graph. Standard errors are displayed in yellow. The number of proteins that have a residue at a specific position is shown with a black line. TM: transmembrane.</p

Evolutionarily conserved motif region in the Synaptotagmin 14 linker region.

<p>The upper panel shows a graphical representation of whole Synaptotagmin 14 protein. The transmembrane region (TM), the linker and the two C2 domains are shown. The lower panel shows the first 120 residues of an alignment of synaptotagmin 14 with identified orthologues. Red bars indicate Relative Local Conservation (RLC) and the blue bars indicate IUPred disorder scores. The brown background shows an ordered part (IUPred score ><0.3) around the transmembrane region.</p

Frequency of conserved motifs.

<p>The frequency (blue line) depicts the number of instances that a specific residue position falls inside a predicted motif. Disorder profile of single-pass transmembrane proteins when the membrane region was included in the analysis is shown in red, with standard errors displayed in yellow. The number of proteins that have a residue at a specific position is shown with a black line.</p

Amino acid composition.

<p>Standard error bars plotted on the graph are very close to the mean values. EC: extracellular. IC: intracellular.</p

Design and Evaluation of Antimalarial Peptides Derived from Prediction of Short Linear Motifs in Proteins Related to Erythrocyte Invasion

<div><p>The purpose of this study was to investigate the blood stage of the malaria causing parasite, <i>Plasmodium falciparum</i>, to predict potential protein interactions between the parasite merozoite and the host erythrocyte and design peptides that could interrupt these predicted interactions. We screened the <i>P. falciparum</i> and human proteomes for computationally predicted short linear motifs (SLiMs) in cytoplasmic portions of transmembrane proteins that could play roles in the invasion of the erythrocyte by the merozoite, an essential step in malarial pathogenesis. We tested thirteen peptides predicted to contain SLiMs, twelve of them palmitoylated to enhance membrane targeting, and found three that blocked parasite growth in culture by inhibiting the initiation of new infections in erythrocytes. Scrambled peptides for two of the most promising peptides suggested that their activity may be reflective of amino acid properties, in particular, positive charge. However, one peptide showed effects which were stronger than those of scrambled peptides. This was derived from human red blood cell glycophorin-B. We concluded that proteome-wide computational screening of the intracellular regions of both host and pathogen adhesion proteins provides potential lead peptides for the development of anti-malarial compounds.</p></div

Palmitoylated peptides designed around cytoplasmic SLiMs from transmembrane proteins.

<p>Peptides selected for testing, the peptide sequence showing palmitoylation (pal) acetylation (Ac) and amidation (NH₂) and the protein from which the peptide originated.</p><p>Palmitoylated peptides designed around cytoplasmic SLiMs from transmembrane proteins.</p

Dose-response curves for selected peptides.

<p>Peptides 5, 7, 10, 11, 12, 13 and DMSO were evaluated at 48 hours (a) and at 72 hours (b). Data are means of three experiments in duplicate and vertical bars indicate standard errors.</p

Growth inhibition by scrambled peptides.

<p>Peptides 5, 10 and 12 and their scrambled peptides were tested in three concentrations, 100 <i>μ</i>M (left bar), 10 <i>μ</i>M (middle bar) and 1 <i>μ</i>M (right bar) at 48 hours (a) and at 72 hours (b). Data are means of three experiments in duplicate and vertical bars indicate standard errors.</p