The oligodeoxynucleotide sequences corresponding to never-expressed peptide motifs are mainly located in the non-coding strand

Abstract

BackgroundWe study the usage of specific peptide platforms in protein composition. Using the pentapeptide as a unit of length, we find that in the universal proteome many pentapeptides are heavily repeated (even thousands of times), whereas some are quite rare, and a small number do not appear at all. To understand the physico-chemical-biological basis underlying peptide usage at the proteomic level, in this study we analyse the energetic costs for the synthesis of rare and never-expressed versus frequent pentapeptides. In addition, we explore residue bulkiness, hydrophobicity, and codon number as factors able to modulate specific peptide frequencies. Then, the possible influence of amino acid composition is investigated in zero- and high-frequency pentapeptide sets by analysing the frequencies of the corresponding inverse-sequence pentapeptides. As a final step, we analyse the pentadecamer oligodeoxynucleotide sequences corresponding to the never-expressed pentapeptides.ResultsWe find that only DNA context-dependent constraints (such as oligodeoxynucleotide sequence location in the minus strand, introns, pseudogenes, frameshifts, etc.) provide a coherent mechanistic platform to explain the occurrence of never-expressed versus frequent pentapeptides in the protein world.ConclusionsThis study is of importance in cell biology. Indeed, the rarity (or lack of expression) of specific 5-mer peptide modules implies the rarity (or lack of expression) of the corresponding n-mer peptide sequences (with n < 5), so possibly modulating protein compositional trends. Moreover the data might further our understanding of the role exerted by rare pentapeptide modules as critical biological effectors in protein-protein interactions.

Hydrophobicity and the Physico-Chemical Basis of Immunotolerance

“…When compared to frequent pentapeptides, the immunogenic low-/zero-frequency pentapeptides are in general endowed with higher hydrophobicity levels, as shown in Figure 5 [7]. That is, the hydrophobic methionine (M), phenylalanine (F), tryptophan (W), and tyrosine (Y) are main components of the immunogenic, low-/ zero-frequency antigen pentapeptides, while, conversely, the non-immunogenic, frequent pentapeptides are mainly composed of hydrophilic aa residues.…”

“…Such a concept arose from the fact that frequent peptide sequences are mostly unable to evoke an immune response, whilst rare peptide sequences are specifically targeted by immune responses and appear to be associated with immunogenicity [6, and references therein]. Moreover, from the chemical-physical point of view, specific properties such as hydrophilicity and hydrophobicity had been shown to characterize the tolerized frequent peptide sequences and the immunogenic rare peptide, respectively [7].…”

Evidence for a vast peptide overlap between West Nile virus and human proteomes

“…From the evolutionary point of view, a thorough analysis of the common (or unique) phenetic links among microbial and mammalian organisms might help understand relationships and common evolutionary roots between distant organisms such as microbes and humans. Indeed, as already observed , usage of frequent (or rare) 5‐mer peptide modules implies a frequent (or rare) expression of the corresponding n‐mer peptide sequences (with n > 5), thus possibly modulating common protein compositional trends in protein evolution among different organisms.…”

A peptide talk between JC virus and the human host: from silent infection to autoimmunity

“…Rare pentapeptides are numerically defined by five (or fewer) perfect matches to the host proteome. (29) JCV peptide epitopes were derived from Immune Epitope DataBase (IEDB, http://www.immuneepitope. org).…”