title: Comparative analysis of protein unfoldedness in human housekeeping and non-housekeeping proteins.
abstract: Absence of any regular structure is increasingly being observed in structural studies of proteins. These disordered regions or random coils, which have been observed under physiological conditions, are indicators of protein plasticity. The wide variety of interactions possible due to the flexibility of these 'natively disordered' regions confers functional advantage to the protein and the organism in general. This concept is underscored by the increasing proportion of intrinsically unstructured proteins seen with the ascension in the complexity of the organisms. The 'natively unfolded/disordered' state of the protein can be predicted utilizing Uversky's or Dunker's algorithm. We utilized Uversky's prediction scheme and based on the unique position of a protein in the charge-hydrophobicity plot, a derived net score was used to predict the overall disorder of the human housekeeping and non-housekeeping proteins. Substantial numbers of proteins in both the classes were predicted to be unfolded. However, comparative genomic analysis of predicted unfolded Homo sapiens proteins with homologues in Caenorhabditis elegans, Drosophila melanogaster and Mus musculus revealed significant increase in unfoldedness in non-housekeeping proteins in comparison with housekeeping proteins. Our analysis in the evolutionary context suggests addition or substitution of amino acid residues which favour unfoldedness in non-housekeeping proteins compared to housekeeping proteins.
authors.affiliation: Institute of Genomics and Integrative Biology (CSIR), Delhi University Campus, Mall Road, Delhi 110 007, India.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Pandey
authors.forename: Mythily
authors.initials: M
authors.lastname: Ganapathi
authors.forename: Kaushal
authors.initials: K
authors.lastname: Kumar
authors.forename: Dipayan
authors.initials: D
authors.lastname: Dasgupta
authors.forename: Sushanta Kumar
authors.initials: SK
authors.lastname: Das Sutar
authors.forename: Debasis
authors.initials: D
authors.lastname: Dash
mesh_terms: D000465:Algorithms; D000818:Animals; D017173:Caenorhabditis elegans; D017124:Conserved Sequence; D004331:Drosophila melanogaster; D019143:Evolution, Molecular; D006801:Humans; D051379:Mice; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000032:analysis / Q000737:chemistry* / Q000235:genetics*; D016415:Sequence Alignment / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*; D017385:Sequence Homology; D013045:Species Specificity; D013329:Structure-Activity Relationship
chemical_list: D011506:Proteins