Emergence and evolution of an interaction between intrinsically disordered proteins

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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 (K_d~5 μM). At the time of the first vertebrate-specific whole genome duplication the affinity had increased (K_d~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

The following previously published data sets were used

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Article and author information

Author details

Greta Hultqvist

Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden

For correspondence
greta.hultqvist@pubcare.uu.se

Competing interests
The authors declare that no competing interests exist.
Emma Åberg

Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden

Competing interests
The authors declare that no competing interests exist.
Carlo Camilloni

Department of Chemistry, University of Cambridge, Cambridge, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Gustav N Sundell

Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden

Competing interests
The authors declare that no competing interests exist.
Eva Andersson

Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden

Competing interests
The authors declare that no competing interests exist.
Jakob Dogan

Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden

Competing interests
The authors declare that no competing interests exist.
Celestine N chi

Laboratory of Physical Chemistry, ETH Zürich, Zürich, Switzerland

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-4154-2378
Michele Vendruscolo

Department of Chemistry, University of Cambridge, Cambridge, United Kingdom

For correspondence
mv245@cam.ac.uk

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-3616-1610
Per Jemth

Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden

For correspondence
Per.Jemth@imbim.uu.se

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-1516-7228

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.

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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.