Intrinsic unstructuredness and abundance of PEST motifs in eukaryotic proteomes

• Published in: Proteins, structure, function, and bioinformatics Vol. 62; no. 2; pp. 309 - 315
• Main Authors: Singh, Gajinder Pal, Ganapathi, Mythily, Sandhu, Kuljeet Singh, Dash, Debasis
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.02.2006
• Subjects: Amino Acid Sequence; Animals; Genome; Humans; PEST motifs; protein degradation signals; Protein Denaturation; protein disorder; Protein Folding; protein unfoldedness; Proteins - chemistry; Proteins - genetics; proteolysis; Proteome; Surface Properties; unstructured regions
• ISSN: 0887-3585; 1097-0134
• DOI: 10.1002/prot.20746

The study of unfolded protein regions has gained importance because of their prevalence and important roles in various cellular functions. These regions have characteristically high net charge and low hydrophobicity. The amino acid sequence determines the intrinsic unstructuredness of a region and, therefore, efforts are ongoing to delineate the sequence motifs, which might contribute to protein disorder. We find that PEST motifs are enriched in the characterized disordered regions as compared with globular ones. Analysis of representative PDB chains revealed very few structures containing PEST sequences and the majority of them lacked regular secondary structure. A proteome‐wide study in completely sequenced eukaryotes with predicted unfolded and folded proteins shows that PEST proteins make up a large fraction of unfolded dataset as compared with the folded proteins. Our data also reveal the prevalence of PEST proteins in eukaryotic proteomes (∼25%). Functional classification of the PEST‐containing proteins shows an over‐ and under‐representation in proteins involved in regulation and metabolism, respectively. Furthermore, our analysis shows that predicted PEST regions do not exhibit any preference to be localized in the C terminals of proteins, as reported earlier. Proteins 2006. © 2005 Wiley‐Liss, Inc.