Flexible nets

The roles of intrinsic disorder in protein interaction networks

A. Dunker, Marc S. Cortese, Pedro Romero, Lilia M. Iakoucheva, Vladimir N. Uversky

Research output: Contribution to journalArticle

749 Citations (Scopus)

Abstract

Proteins participate in complex sets of interactions that represent the mechanistic foundation for much of the physiology and function of the cell. These protein-protein interactions are organized into exquisitely complex networks. The architecture of protein-protein interaction networks was recently proposed to be scale-free, with most of the proteins having only one or two connections but with relatively fewer 'hubs' possessing tens, hundreds or more links. The high level of hub connectivity must somehow be reflected in protein structure. What structural quality of hub proteins enables them to interact with large numbers of diverse targets? One possibility would be to employ binding regions that have the ability to bind multiple, structurally diverse partners. This trait can be imparted by the incorporation of intrinsic disorder in one or both partners. To illustrate the value of such contributions, this review examines the roles of intrinsic disorder in protein network architecture. We show that there are three general ways that intrinsic disorder can contribute: First, intrinsic disorder can serve as the structural basis for hub protein promiscuity; secondly, intrinsically disordered proteins can bind to structured hub proteins; and thirdly, intrinsic disorder can provide flexible linkers between functional domains with the linkers enabling mechanisms that facilitate binding diversity. An important research direction will be to determine what fraction of protein-protein interaction in regulatory networks relies on intrinsic disorder.

Original languageEnglish
Pages (from-to)5129-5148
Number of pages20
JournalFEBS Journal
Volume272
Issue number20
DOIs
StatePublished - Oct 2005

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Protein Interaction Maps
Proteins
Intrinsically Disordered Proteins
Cell Physiological Phenomena
Physiology
Complex networks
Network architecture

ASJC Scopus subject areas

  • Biochemistry

Cite this

Flexible nets : The roles of intrinsic disorder in protein interaction networks. / Dunker, A.; Cortese, Marc S.; Romero, Pedro; Iakoucheva, Lilia M.; Uversky, Vladimir N.

In: FEBS Journal, Vol. 272, No. 20, 10.2005, p. 5129-5148.

Research output: Contribution to journalArticle

Dunker, A, Cortese, MS, Romero, P, Iakoucheva, LM & Uversky, VN 2005, 'Flexible nets: The roles of intrinsic disorder in protein interaction networks', FEBS Journal, vol. 272, no. 20, pp. 5129-5148. https://doi.org/10.1111/j.1742-4658.2005.04948.x
Dunker, A. ; Cortese, Marc S. ; Romero, Pedro ; Iakoucheva, Lilia M. ; Uversky, Vladimir N. / Flexible nets : The roles of intrinsic disorder in protein interaction networks. In: FEBS Journal. 2005 ; Vol. 272, No. 20. pp. 5129-5148.
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