title: Intrinsic disorder is a common feature of hub proteins from four eukaryotic interactomes.
abstract: Recent proteome-wide screening approaches have provided a wealth of information about interacting proteins in various organisms. To test for a potential association between protein connectivity and the amount of predicted structural disorder, the disorder propensities of proteins with various numbers of interacting partners from four eukaryotic organisms (Caenorhabditis elegans, Saccharomyces cerevisiae, Drosophila melanogaster, and Homo sapiens) were investigated. The results of PONDR VL-XT disorder analysis show that for all four studied organisms, hub proteins, defined here as those that interact with > or = 10 partners, are significantly more disordered than end proteins, defined here as those that interact with just one partner. The proportion of predicted disordered residues, the average disorder score, and the number of predicted disordered regions of various lengths were higher overall in hubs than in ends. A binary classification of hubs and ends into ordered and disordered subclasses using the consensus prediction method showed a significant enrichment of wholly disordered proteins and a significant depletion of wholly ordered proteins in hubs relative to ends in worm, fly, and human. The functional annotation of yeast hubs and ends using GO categories and the correlation of these annotations with disorder predictions demonstrate that proteins with regulation, transcription, and development annotations are enriched in disorder, whereas proteins with catalytic activity, transport, and membrane localization annotations are depleted in disorder. The results of this study demonstrate that intrinsic structural disorder is a distinctive and common characteristic of eukaryotic hub proteins, and that disorder may serve as a determinant of protein interactivity.
authors.affiliation: Laboratory of Statistical Genetics, The Rockefeller University, New York, New York, USA.
authors.forename: Chad
authors.initials: C
authors.lastname: Haynes
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Oldfield
authors.forename: Fei
authors.initials: F
authors.lastname: Ji
authors.forename: Niels
authors.initials: N
authors.lastname: Klitgord
authors.forename: Michael E
authors.initials: ME
authors.lastname: Cusick
authors.forename: Predrag
authors.initials: P
authors.lastname: Radivojac
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Uversky
authors.forename: Marc
authors.initials: M
authors.lastname: Vidal
authors.forename: Lilia M
authors.initials: LM
authors.lastname: Iakoucheva
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology; D029721:Drosophila Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051959:ELAV Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D000067777:ELAV-Like Protein 2; D006801:Humans; D008025:Ligases / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D029721:Drosophila Proteins; D051959:ELAV Proteins; D000067777:ELAV-Like Protein 2; C086811:ELAVL2 protein, human; D029701:Saccharomyces cerevisiae Proteins; D008025:Ligases; C452202:HUB1 protein, S cerevisiae