Journal ArticleDOI
Disorder and sequence repeats in hub proteins and their implications for network evolution.
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TLDR
This view contradicts the prevailing view that scaling in protein interactomes arose from gene duplication and preferential attachment of equivalent proteins and proposes 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 become specialized in network organization.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.read more
Citations
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Intrinsically Disordered Proteins in Human Diseases: Introducing the D2 Concept
TL;DR: Overall, intriguing interconnections among intrinsic disorder, cell signaling, and human diseases suggest that protein conformational diseases may result not only from protein misfolding, but also from misidentification, missignaling, and unnatural or nonnative folding.
Journal ArticleDOI
Understanding protein non-folding.
TL;DR: This review describes the family of intrinsically disordered proteins, members of which fail to form rigid 3-D structures under physiological conditions, either along their entire lengths or only in localized regions.
Journal ArticleDOI
Function and structure of inherently disordered proteins
TL;DR: Topics concerning proteins inherently lacking 3D structure are discussed, including their prediction from amino acid sequence, their enrichment in eukaryotes compared to prokaryotes, their more rapid evolution compared to structured proteins, their organization into specific groups, their structural preferences, their half-lives in cells, and their involvement in diseases.
Journal ArticleDOI
Intrinsic Disorder and Functional Proteomics
Predrag Radivojac,Lilia M. Iakoucheva,Christopher J. Oldfield,Zoran Obradovic,Vladimir N. Uversky,Vladimir N. Uversky,A. Keith Dunker +6 more
TL;DR: The recent advances in the prediction of intrinsically disordered proteins and the use of protein disorder prediction in the fields of molecular biology and bioinformatics are reviewed here, especially with regard to protein function.
Journal ArticleDOI
The unfoldomics decade: an update on intrinsically disordered proteins
A. Keith Dunker,Christopher J. Oldfield,Jingwei Meng,Pedro Romero,Jack Y. Yang,Jessica Walton Chen,Vladimir Vacic,Zoran Obradovic,Vladimir N. Uversky,Vladimir N. Uversky +9 more
TL;DR: The goal is to review the key discoveries and to weave these discoveries together to support novel approaches for understanding sequence-function relationships.
References
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Journal ArticleDOI
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Journal ArticleDOI
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TL;DR: Many gene sequences in eukaryotic genomes encode entire proteins or large segments of proteins that lack a well-structured three-dimensional fold, whereas others constitute flexible linkers that have a role in the assembly of macromolecular arrays.