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Int. J. Mol. Sci. 2018, 19(11), 3315; https://doi.org/10.3390/ijms19113315

Co-Evolution of Intrinsically Disordered Proteins with Folded Partners Witnessed by Evolutionary Couplings

1,*,†, 2,† and 1,3,*
1
Research Centre for Natural Sciences of the Hungarian Academy of Sciences, Institute of Enzymology, 1117 Budapest, Hungary
2
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
3
Center for Structural Biology, Flanders Institute for Biotechnology (VIB), Vrije Universiteit Brussel, 1050 Brussels, Belgium
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 30 September 2018 / Revised: 19 October 2018 / Accepted: 22 October 2018 / Published: 25 October 2018
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Abstract

Although improved strategies for the detection and analysis of evolutionary couplings (ECs) between protein residues already enable the prediction of protein structures and interactions, they are mostly restricted to conserved and well-folded proteins. Whereas intrinsically disordered proteins (IDPs) are central to cellular interaction networks, due to the lack of strict structural constraints, they undergo faster evolutionary changes than folded domains. This makes the reliable identification and alignment of IDP homologs difficult, which led to IDPs being omitted in most large-scale residue co-variation analyses. By preforming a dedicated analysis of phylogenetically widespread bacterial IDP–partner interactions, here we demonstrate that partner binding imposes constraints on IDP sequences that manifest in detectable interprotein ECs. These ECs were not detected for interactions mediated by short motifs, rather for those with larger IDP–partner interfaces. Most identified coupled residue pairs reside close (<10 Å) to each other on the interface, with a third of them forming multiple direct atomic contacts. EC-carrying interfaces of IDPs are enriched in negatively charged residues, and the EC residues of both IDPs and partners preferentially reside in helices. Our analysis brings hope that IDP–partner interactions difficult to study could soon be successfully dissected through residue co-variation analysis. View Full-Text
Keywords: intrinsically disordered; disordered protein; structural disorder; correlated mutations; co-evolution; evolutionary couplings; residue co-variation; interaction surface; residue contact network intrinsically disordered; disordered protein; structural disorder; correlated mutations; co-evolution; evolutionary couplings; residue co-variation; interaction surface; residue contact network
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Pancsa, R.; Zsolyomi, F.; Tompa, P. Co-Evolution of Intrinsically Disordered Proteins with Folded Partners Witnessed by Evolutionary Couplings. Int. J. Mol. Sci. 2018, 19, 3315.

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