Disorder and sequence repeats in hub proteins and their implications for network evolution.

TitleDisorder and sequence repeats in hub proteins and their implications for network evolution.
Publication TypeJournal Article
Year of Publication2006
AuthorsDosztányi, Z., J. Chen, K. A Dunker, I. Simon, and P. Tompa
JournalJ Proteome Res
Volume5
Issue11
Pagination2985-95
Date Published2006 Nov
ISSN1535-3893
KeywordsAmino Acid Sequence, Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Drosophila melanogaster, Drosophila Proteins, Evolution, Molecular, Genome, Humans, Nerve Net, Proteins, Repetitive Sequences, Amino Acid, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sequence Homology, Amino Acid
Abstract

Protein interaction networks display approximate scale-free topology, in which hub proteins that interact with a large number of other proteins determine the overall organization of the network. In this study, we aim to determine whether hubs are distinguishable from other networked proteins by specific sequence features. Proteins of different connectednesses were compared in the interaction networks of Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis elegans, and Homo sapienswith respect to the distribution of predicted structural disorder, sequence repeats, low complexity regions, and chain length. Highly connected proteins ("hub proteins") contained significantly more of, and greater proportion of, these sequence features and tended to be longer overall as compared to less connected proteins. These sequence features provide two different functional means for realizing multiple interactions: (1) extended interaction surface and (2) flexibility and adaptability, providing a mechanism for the same region to bind distinct partners. Our view contradicts the prevailing view that scaling in protein interactomes arose from gene duplication and preferential attachment of equivalent proteins. We propose an alternative evolutionary network specialization process, in which certain components of the protein interactome improved their fitness for binding by becoming longer or accruing regions of disorder and/or internal repeats and have therefore become specialized in network organization.

DOI10.1021/pr060171o
Alternate JournalJ. Proteome Res.
PubMed ID17081050
Grant ListISRF 067595 / / Wellcome Trust / United Kingdom
R01 LM007688 / LM / NLM NIH HHS / United States