Emergence and evolution of an interaction between intrinsically disordered proteins
- Uppsala University, Sweden
- University of Cambridge, United Kingdom
- ETH Zürich, Switzerland
Abstract
Protein-protein interactions involving intrinsically disordered proteins are important for cellular function and common in all organisms. However, it is not clear how such interactions emerge and evolve on a molecular level. We performed phylogenetic reconstruction, resurrection and biophysical characterization of two interacting disordered protein domains, CID and NCBD. CID appeared after the divergence of protostomes and deuterostomes 450-600 million years ago, while NCBD was present in the protostome/deuterostome ancestor. The most ancient CID/NCBD formed a relatively weak complex (Kd~5 μM). At the time of the first vertebrate-specific whole genome duplication the affinity had increased (Kd~200 nM) and was maintained in further speciation. Experiments together with molecular modeling using NMR chemical shifts suggest that new interactions involving intrinsically disordered proteins may evolve via a low affinity complex which is optimized by modulating direct interactions as well as dynamics, while tolerating several potentially disruptive mutations.
Data availability
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EnsemblPublicly available at the Ensembl.
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Japanese lamprey genome projectPublicly available at the Japanese Lamprey Genome Project.
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OrcAPublicly available at the Bioinformatics and Evolutionary Genomics.
Article and author information
Author details
Michele Vendruscolo
Funding
Vetenskapsrådet
- Per Jemth
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jeffery W Kelly, The Scripps Research Institute, United States
Version history
- Received: March 15, 2016
- Accepted: March 28, 2017
- Accepted Manuscript published: April 11, 2017 (version 1)
- Version of Record published: May 5, 2017 (version 2)
- Version of Record updated: February 12, 2018 (version 3)
Copyright
© 2017, Hultqvist et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Emergence and evolution of an interaction between intrinsically disordered proteins
eLife 6:e16059.
https://doi.org/10.7554/eLife.16059
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