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PMID: 16884331 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Intrinsic disorder is a common feature of hub proteins from four eukaryotic interactomes.

PLoS computational biology ·Vol. 2 ·No. 8 ·2006-08-04 ·Pages e100

Haynes C, Oldfield CJ, Ji F, Klitgord N, Cusick ME, Radivojac P, Uversky VN, Vidal M, Iakoucheva LM

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.

MeSH Terms
Amino Acids/chemistry Animals Caenorhabditis elegans/chemistry,genetics,metabolism Caenorhabditis elegans Proteins/chemistry,classification,genetics,metabolism Carrier Proteins/chemistry,classification,genetics,metabolism Computational Biology Drosophila Proteins/chemistry,classification,genetics,metabolism Drosophila melanogaster/chemistry,genetics,metabolism ELAV Proteins/chemistry,classification,genetics,metabolism ELAV-Like Protein 2 Humans Ligases/chemistry,classification,genetics,metabolism Models, Molecular Protein Binding Protein Structure, Tertiary Saccharomyces cerevisiae/chemistry,genetics,metabolism Saccharomyces cerevisiae Proteins/chemistry,classification,genetics,metabolism
Chemicals
Amino Acids Caenorhabditis elegans Proteins Carrier Proteins Drosophila Proteins ELAV Proteins ELAV-Like Protein 2 ELAVL2 protein, human Saccharomyces cerevisiae Proteins Ligases HUB1 protein, S cerevisiae
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Haynes Chad
Laboratory of Statistical Genetics, The Rockefeller University, New York, New York, USA.
Oldfield Christopher J
Ji Fei
Klitgord Niels
Cusick Michael E
Radivojac Predrag
Uversky Vladimir N
Vidal Marc
Iakoucheva Lilia M
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Article Info
Journal
PLoS computational biology
Abbr.
PLoS Comput Biol
ISSN
1553-7358
DOI
10.1371/journal.pcbi.0020100
Published
2006-08-04
Epub
2006-00-23
Pages
e100
Language
English
Region
United States
NLM ID
101238922
PMCID
PMC1526461
Subset
IM
Grants
NCI NIH HHS · R33 CA105405 · United States
NCI NIH HHS · U54 CA112952 · United States
NCI NIH HHS · CA105405 · United States
NCI NIH HHS · CA112952 · United States
External Links
PubMed source DOI: 10.1371/journal.pcbi.0020100 PMC Full Text View journal details
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