The Roles of Intrinsic Disorder in Protein Interaction Networks
Document Type
Article
Publication Date
2005
Digital Object Identifier (DOI)
https://doi.org/10.1111/j.1742-4658.2005.04948.x
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.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
The FEBS Journal, v. 272, issue 20, p. 5129-5148
Scholar Commons Citation
Dunker, A. Keith; Cortese, Marc S.; Romero, Pedro R.; Iakoucheva, Lilia M.; and Uversky, Vladimir N., "The Roles of Intrinsic Disorder in Protein Interaction Networks" (2005). Molecular Medicine Faculty Publications. 748.
https://digitalcommons.usf.edu/mme_facpub/748
