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

Zsuzsanna Dosztányi, Jake Chen, A. Dunker, István Simon, Peter Tompa

Research output: Contribution to journalArticle

228 Citations (Scopus)

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 sapiens with 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.

Original languageEnglish
Pages (from-to)2985-2995
Number of pages11
JournalJournal of Proteome Research
Volume5
Issue number11
DOIs
StatePublished - Nov 2006

Fingerprint

Proteins
Protein Interaction Maps
Gene Duplication
Caenorhabditis elegans
Drosophila melanogaster
Chain length
Saccharomyces cerevisiae
Yeast
Genes
Topology

Keywords

  • Disordered protein
  • Hub protein
  • Interaction network
  • Protein-protein interaction
  • Unstructured protein

ASJC Scopus subject areas

  • Genetics
  • Biotechnology
  • Biochemistry

Cite this

Disorder and sequence repeats in hub proteins and their implications for network evolution. / Dosztányi, Zsuzsanna; Chen, Jake; Dunker, A.; Simon, István; Tompa, Peter.

In: Journal of Proteome Research, Vol. 5, No. 11, 11.2006, p. 2985-2995.

Research output: Contribution to journalArticle

Dosztányi, Zsuzsanna ; Chen, Jake ; Dunker, A. ; Simon, István ; Tompa, Peter. / Disorder and sequence repeats in hub proteins and their implications for network evolution. In: Journal of Proteome Research. 2006 ; Vol. 5, No. 11. pp. 2985-2995.
@article{134fc996d3874309902aecc316006769,
title = "Disorder and sequence repeats in hub proteins and their implications for network evolution",
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 sapiens with 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.",
keywords = "Disordered protein, Hub protein, Interaction network, Protein-protein interaction, Unstructured protein",
author = "Zsuzsanna Doszt{\'a}nyi and Jake Chen and A. Dunker and Istv{\'a}n Simon and Peter Tompa",
year = "2006",
month = "11",
doi = "10.1021/pr060171o",
language = "English",
volume = "5",
pages = "2985--2995",
journal = "Journal of Proteome Research",
issn = "1535-3893",
publisher = "American Chemical Society",
number = "11",

}

TY - JOUR

T1 - Disorder and sequence repeats in hub proteins and their implications for network evolution

AU - Dosztányi, Zsuzsanna

AU - Chen, Jake

AU - Dunker, A.

AU - Simon, István

AU - Tompa, Peter

PY - 2006/11

Y1 - 2006/11

N2 - 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 sapiens with 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.

AB - 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 sapiens with 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.

KW - Disordered protein

KW - Hub protein

KW - Interaction network

KW - Protein-protein interaction

KW - Unstructured protein

UR - http://www.scopus.com/inward/record.url?scp=33750999318&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750999318&partnerID=8YFLogxK

U2 - 10.1021/pr060171o

DO - 10.1021/pr060171o

M3 - Article

VL - 5

SP - 2985

EP - 2995

JO - Journal of Proteome Research

JF - Journal of Proteome Research

SN - 1535-3893

IS - 11

ER -