Emergence and evolution of an interaction between intrinsically disordered proteins

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 char...

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Veröffentlicht in:eLife 2017-04, Vol.6
Hauptverfasser: Hultqvist, Greta, Åberg, Emma, Camilloni, Carlo, Sundell, Gustav N, Andersson, Eva, Dogan, Jakob, Chi, Celestine N, Vendruscolo, Michele, Jemth, Per
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Sprache:eng
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Zusammenfassung: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 ( ∼5 µM). At the time of the first vertebrate-specific whole genome duplication, the affinity had increased ( ∼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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.16059